Compositions and methods for modulating utrn expression

ABSTRACT

Aspects of the invention provide single stranded oligonucleotides for activating or enhancing expression of UTRN. Further aspects provide compositions and kits comprising single stranded oligonucleotides for activating or enhancing expression of UTRN. Methods for modulating expression of UTRN using the single stranded oligonucleotides are also provided. Further aspects of the invention provide methods for selecting a candidate oligonucleotide for activating or enhancing expression of UTRN.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit under 35 U.S.C. §119(e) of U.S.Provisional Application No. 61/647,886, entitled “COMPOSITIONS ANDMETHODS FOR MODULATING UTRN EXPRESSION”, filed May 16, 2012, which isincorporated herein by reference in its entirety.

FIELD OF THE INVENTION

The invention relates to oligonucleotide based compositions, as well asmethods of using oligonucleotide based compositions for treatingdisease.

BACKGROUND OF THE INVENTION

Muscular dystrophy (MD) is a group of inherited diseases characterizedby damage to muscle fibers and includes Duchenne's muscular dystrophy,Becker's muscular dystrophy, and myotonic dystrophy. Duchenne's musculardystrophy (DMD) is a recessive X-linked form of muscular dystrophyresulting from mutation in the dystrophin gene. Dystrophin is astructural component of muscle tissue that stabilized the dystroglycancomplex and is important for connecting the cytoskeleton of musclefibers to the basal lamina. When dystrophin is mutated, excess calciumpenetrates the cell membrane of muscle cells, causing mitochondrialdamage from an influx of water. This mitochondrial damage results inincreased oxidative stress and cell death, leading to necrosis of musclefibers. The destruction of muscle fibers causes the symptoms of DMD,including gradual muscular degeneration, gait ataxia, difficultybreathing, and eventually, death. Becker's Muscular dystrophy (BMD) is aless severe form of muscular dystrophy characterized by progressivemuscle weakness in the legs and pelvis. BMD is also caused by a mutationin dystrophin, but unlike DMD, some functional dystrophin is present.Myotonic dystrophy is an autosomal dominant disease characterized bywasting of the muscles, cataracts, heart conduction defects, endocrinechanges, and myotonia. Utrophin, encoded by the UTRN gene, is acomponent of the cytoskeleton located at the neuromuscular synapse andmyotendinous junctions, and is involved in membrane maintenance andacetylchoine receptor clustering. Utrophin has homology with dystrophin,especially in the actin binding domain, and can partially compensate fora lack of dystrophin in mice.

SUMMARY OF THE INVENTION

Aspects of the invention disclosed herein provide methods andcompositions that are useful for overexpression of Utrophin (UTRN) forthe treatment and/or prevention of diseases associated with reducedexpression of UTRN, or for which enhanced expression of UTRN would bebeneficial (e.g., muscular dystrophies, including Duchenne musculardystrophy (DMD), Becker Muscular Dystrophy (BMD), and myotonicdystrophy). In certain aspects, the invention provides methods andcompositions that are useful for upregulating UTRN in a cell. In someembodiments, the methods and compositions are useful for the treatmentand/or prevention (e.g., reducing the risk or delaying the onset) ofmuscular dystrophies, including DMD, BMD, and myotonic dystrophy. Insome embodiments, single stranded oligonucleotides are provided thattarget a PRC2-associated region of a UTRN gene (e.g., human UTRN) andthereby cause upregulation of the gene. In some embodiments, singlestranded oligonucleotides are provided that target a PRC2-associatedregion of the gene encoding UTRN. In some embodiments, these singlestranded oligonucleotides activate or enhance expression of UTRN byrelieving or preventing PRC2 mediated repression of UTRN.

Further aspects of the invention provide methods for selectingoligonucleotides for activating or enhancing expression of UTRN. In someembodiments, methods are provided for selecting a set ofoligonucleotides that is enriched in candidates (e.g., compared with arandom selection of oligonucleotides) for activating or enhancingexpression of UTRN. Accordingly, the methods may be used to establishsets of clinical candidates that are enriched in oligonucleotides thatactivate or enhance expression of UTRN. Such libraries may be utilized,for example, to identify lead oligonucleotides for developingtherapeutics to treat UTRN. Furthermore, in some embodiments,oligonucleotide chemistries are provided that are useful for controllingthe pharmacokinetics, biodistribution, bioavailability and/or efficacyof the single stranded oligonucleotides for activating expression ofUTRN.

According to some aspects of the invention single strandedoligonucleotides are provided that have a region of complementarity thatis complementarity with (e.g., at least 8 consecutive nucleotides of) aPRC2-associated region of a UTRN gene, e.g., a PRC2-associated region ofthe nucleotide sequence set forth as SEQ ID NO: 1 or 2. In someembodiments, the oligonucleotide has at least one of the followingfeatures: a) a sequence that is 5′X-Y-Z, in which X is any nucleotideand in which X is at the 5′ end of the oligonucleotide, Y is anucleotide sequence of 6 nucleotides in length that is not a human seedsequence of a microRNA, and Z is a nucleotide sequence of 1 to 23nucleotides in length; b) a sequence that does not comprise three ormore consecutive guanosine nucleotides; c) a sequence that has less thana threshold level of sequence identity with every sequence ofnucleotides, of equivalent length to the second nucleotide sequence,that are between 50 kilobases upstream of a 5′-end of an off-target geneand 50 kilobases downstream of a 3′-end of the off-target gene; d) asequence that is complementary to a PRC2-associated region that encodesan RNA that forms a secondary structure comprising at least two singlestranded loops; and e) a sequence that has greater than 60% G-C content.In some embodiments, the single stranded oligonucleotide has at leasttwo of features a), b), c), d), and e), each independently selected. Insome embodiments, the single stranded oligonucleotide has at least threeof features a), b), c), d), and e), each independently selected. In someembodiments, the single stranded oligonucleotide has at least four offeatures a), b), c), d), and e), each independently selected. In someembodiments, the single stranded oligonucleotide has each of featuresa), b), c), d), and e). In certain embodiments, the oligonucleotide hasthe sequence 5′X-Y-Z, in which the oligonucleotide is 8-50 nucleotidesin length.

According to some aspects of the invention, single strandedoligonucleotides are provided that have a sequence X-Y-Z, in which X isany nucleotide, Y is a nucleotide sequence of 6 nucleotides in lengththat is not a seed sequence of a human microRNA, and Z is a nucleotidesequence of 1 to 23 nucleotides in length, in which the single strandedoligonucleotide is complementary with a PRC2-associated region of a UTRNgene, e.g., a PRC2-associated region of the nucleotide sequence setforth as SEQ ID NO: 1 or 2. In some aspects of the invention, singlestranded oligonucleotides are provided that have a sequence 5′-X-Y-Z, inwhich X is any nucleotide, Y is a nucleotide sequence of 6 nucleotidesin length that is not a seed sequence of a human microRNA, and Z is anucleotide sequence of 1 to 23 nucleotides in length, in which thesingle stranded oligonucleotide is complementary with at least 8consecutive nucleotides of a PRC2-associated region of a UTRN gene,e.g., a PRC2-associated region of the nucleotide sequence set forth asSEQ ID NO: 1 or 2. In some embodiments, Y is a sequence selected fromTable 1. In some embodiments, the PRC2-associated region is a sequencelisted in any one of SEQ ID NOS: 5 to 462.

In some embodiments, the single stranded oligonucleotide comprises anucleotide sequence as set forth in any one of SEQ ID NOS: 463 to497728, or a fragment thereof that is at least 8 nucleotides. In someembodiments, the single stranded oligonucleotide comprises a nucleotidesequence as set forth in any one of SEQ ID NOS: 463 to 497728, in whichthe 5′ end of the nucleotide sequence provided is the 5′ end of theoligonucleotide. In some embodiments, the region of complementarity(e.g., the at least 8 consecutive nucleotides) is also present withinthe nucleotide sequence set forth as SEQ ID NO: 3 or 4.

In some embodiments, the single stranded oligonucleotide comprises anucleotide sequence as set forth in any one of SEQ ID NOS: 463 to497728. In some embodiments, the single stranded oligonucleotidecomprises a fragment of at least 8 nucleotides of a nucleotide sequenceas set forth in any one of SEQ ID NOS: 463 to 497728.

In some embodiments, the PRC2-associated region is a sequence listed inany one of SEQ ID NOS: 5 to 328. In some embodiments, the singlestranded oligonucleotide comprises a nucleotide sequence as set forth inany one of SEQ ID NOS: 463-307980 or a fragment thereof that is at least8 nucleotides. In some embodiments, the single stranded oligonucleotidecomprises a nucleotide sequence as set forth in any one of SEQ ID NOS:463-307980, wherein the 5′ end of the nucleotide sequence provided isthe 5′ end of the oligonucleotide. In some embodiments, the at least 8consecutive nucleotides are also present within the nucleotide sequenceset forth as SEQ ID NO: 3.

In some embodiments, the PRC2-associated region is a sequence listed inany one of SEQ ID NOS: 329 to 462. In some embodiments, the singlestranded oligonucleotide comprises a nucleotide sequence as set forth inany one of SEQ ID NOS: 306018-497728 or a fragment thereof that is atleast 8 nucleotides. In some embodiments, the single strandedoligonucleotide comprises a nucleotide sequence as set forth in any oneof SEQ ID NOS: 306018-497728 wherein the 5′ end of the nucleotidesequence provided is the 5′ end of the oligonucleotide. In someembodiments, the at least 8 consecutive nucleotides are present withinthe nucleotide sequence set forth as SEQ ID NO: 4. In some embodiments,a single stranded oligonucleotide comprises a nucleotide sequence as setforth in Table 4. In some embodiments, the single strandedoligonucleotide comprises a fragment of at least 8 nucleotides of anucleotide sequence as set forth in Table 4. In some embodiments, asingle stranded oligonucleotide consists of a nucleotide sequence as setforth in Table 4.

In some embodiments, the single stranded oligonucleotide does notcomprise three or more consecutive guanosine nucleotides. In someembodiments, the single stranded oligonucleotide does not comprise fouror more consecutive guanosine nucleotides.

In some embodiments, the single stranded oligonucleotide is 8 to 30nucleotides in length. In some embodiments, the single strandedoligonucleotide is up to 50 nucleotides in length. In some embodiments,the single stranded oligonucleotide is 8 to 10 nucleotides in length andall but 1, 2, or 3 of the nucleotides of the complementary sequence ofthe PRC2-associated region are cytosine or guanosine nucleotides.

In some embodiments, the single stranded oligonucleotide iscomplementary with at least 8 consecutive nucleotides of aPRC2-associated region of a UTRN gene, e.g., a PRC2-associated region ofa nucleotide sequence set forth as SEQ ID NO: 1 or 2, in which thenucleotide sequence of the single stranded oligonucleotide comprises oneor more of a nucleotide sequence selected from the group consisting of

(a) (X)Xxxxxx, (X)xXxxxx, (X)xxXxxx, (X)xxxXxx, (X)xxxxXx and (X)xxxxxX,

(b) (X)XXxxxx, (X)XxXxxx, (X)XxxXxx, (X)XxxxXx, (X)XxxxxX, (X)xXXxxx,(X)xXxXxx, (X)xXxxXx, (X)xXxxxX, (X)xxXXxx, (X)xxXxXx, (X)xxXxxX,(X)xxxXXx, (X)xxxXxX and (X)xxxxXX,

(c) (X)XXXxxx, (X)xXXXxx, (X)xxXXXx, (X)xxxXXX, (X)XXxXxx, (X)XXxxXx,(x)XXxxxX, (X)xXXxXx, (X)xXXxxX, (X)xxXXxX, (X)XxXXxx, (X)XxxXXx(x)XxxxXX, (X)xXxXXx, (X)xXxxXX, (X)xxXxXX, (X)xXxXxX and (X)XxXxXx,

(d) (X)xxXXX, (X)xXxXXX, (X)xXXxXX, (X)xXXXxX, (X)xXXXXx, (X)XxxXXXX,(X)XxXxXX, (X)XxXXxX, (X)XxXXx, (X)XXxxXX, (X)XXxXxX, (x)XXxXXx,(X)XXXxxX, (X)XXXxXx, and (X)XXXXxx,

(e) (X)xXXXXX, (X)XxXXXX, (X)XXxXXX, (X)XXXxXX, (X)XXXXxX and (x)XXXXXx,and

(f) XXXXXX, XxXXXXX, XXxXXXX, XXXxXXX, XXXXxXX, XXXXXxX and XXXXXXx,wherein “X” denotes a nucleotide analogue, (X) denotes an optionalnucleotide analogue, and “x” denotes a DNA or RNA nucleotide unit.

In some embodiments, at least one nucleotide of the oligonucleotide is anucleotide analogue. In some embodiments, the at least one nucleotideanalogue results in an increase in Tm of the oligonucleotide in a rangeof 1 to 5° C. compared with an oligonucleotide that does not have the atleast one nucleotide analogue.

In some embodiments, at least one nucleotide of the oligonucleotidecomprises a 2′ O-methyl. In some embodiments, each nucleotide of theoligonucleotide comprises a 2′ O-methyl. In some embodiments, theoligonucleotide comprises at least one ribonucleotide, at least onedeoxyribonucleotide, or at least one bridged nucleotide. In someembodiments, the bridged nucleotide is a LNA nucleotide, a cEtnucleotide or a ENA modified nucleotide. In some embodiments, eachnucleotide of the oligonucleotide is a LNA nucleotide.

In some embodiments, the nucleotides of the oligonucleotide comprisealternating deoxyribonucleotides and 2′-fluoro-deoxyribonucleotides. Insome embodiments, the nucleotides of the oligonucleotide comprisealternating deoxyribonucleotides and 2′-O-methyl nucleotides. In someembodiments, the nucleotides of the oligonucleotide comprise alternatingdeoxyribonucleotides and ENA nucleotide analogues. In some embodiments,the nucleotides of the oligonucleotide comprise alternatingdeoxyribonucleotides and LNA nucleotides. In some embodiments, the 5′nucleotide of the oligonucleotide is a deoxyribonucleotide. In someembodiments, the nucleotides of the oligonucleotide comprise alternatingLNA nucleotides and 2′-O-methyl nucleotides. In some embodiments, the 5′nucleotide of the oligonucleotide is a LNA nucleotide. In someembodiments, the nucleotides of the oligonucleotide comprisedeoxyribonucleotides flanked by at least one LNA nucleotide on each ofthe 5′ and 3′ ends of the deoxyribonucleotides.

In some embodiments, the single stranded oligonucleotide comprisesmodified internucleotide linkages (e.g., phosphorothioateinternucleotide linkages or other linkages) between at least two, atleast three, at least four, at least five or more nucleotides. In someembodiments, the single stranded oligonucleotide comprises modifiedinternucleotide linkages (e.g., phosphorothioate internucleotidelinkages or other linkages) between all nucleotides.

In some embodiments, the nucleotide at the 3′ position of theoligonucleotide has a 3′ hydroxyl group. In some embodiments, thenucleotide at the 3′ position of the oligonucleotide has a 3′thiophosphate. In some embodiments, the single stranded oligonucleotidehas a biotin moiety or other moiety conjugated to its 5′ or 3′nucleotide. In some embodiments, the single stranded oligonucleotide hascholesterol, Vitamin A, folate, sigma receptor ligands, aptamers,peptides, such as CPP, hydrophobic molecules, such as lipids, ASGPR ordynamic polyconjugates and variants thereof at its 5′ or 3′ end.

According to some aspects of the invention compositions are providedthat comprise any of the oligonucleotides disclosed herein, and acarrier. In some embodiments, compositions are provided that compriseany of the oligonucleotides in a buffered solution. In some embodiments,the oligonucleotide is conjugated to the carrier. In some embodiments,the carrier is a peptide. In some embodiments, the carrier is a steroid.According to some aspects of the invention pharmaceutical compositionsare provided that comprise any of the oligonucleotides disclosed herein,and a pharmaceutically acceptable carrier.

According to other aspects of the invention, kits are provided thatcomprise a container housing any of the compositions disclosed herein.

According to some aspects of the invention, methods of increasingexpression of UTRN in a cell are provided. In some embodiments, themethods involve delivering any one or more of the single strandedoligonucleotides disclosed herein into the cell. In some embodiments,delivery of the single stranded oligonucleotide into the cell results ina level of expression of UTRN that is greater (e.g., at least 50%greater) than a level of expression of UTRN in a control cell that doesnot comprise the single stranded oligonucleotide.

According to some aspects of the invention, methods of increasing levelsof UTRN in a subject are provided. According to some aspects of theinvention, methods of treating a condition (e.g., muscular dystrophies,including DMD, BMD, and myotonic dystrophy) associated with decreasedlevels of UTRN in a subject are provided. In some embodiments, themethods involve administering any one or more of the single strandedoligonucleotides disclosed herein to the subject.

BRIEF DESCRIPTION OF TABLES

Table 1: Hexamers that are not seed sequences of human miRNAs

Table 2: Oligonucleotide sequences made for testing. RQ (column 3) andRQ SE (column 4) shows the activity of the oligo relative to a controlwell (usually carrier alone) and the standard error or the triplicatereplicates of the experiment. [oligo] is shown in nanomolar for in vitroexperiments and in milligrams per kilogram of body weight for in vivoexperiments. The Formatted Sequence column sequence of eacholigonucleotide, including any modified nucleotides, is shown in Table4.

Table 3: A listing of oligonucleotide modifications

Table 4: Formatted oligonucleotide sequences made for testing showingnucleotide modifications. The table shows the sequence of the modifiednucleotides, where lnaX represents an LNA nucleotide with 3′phosphorothioate linkage, omeX is a 2′-O-methyl nucleotide, dX is adeoxy nucleotide. An s at the end of a nucleotide code indicates thatthe nucleotide had a 3′ phosphorothioate linkage. The “-Sup” at the endof the sequence marks the fact that the 3′ end lacks either a phosphateor thiophosphate on the 3′ linkage. The Formatted Sequence column showsthe sequence of the oligonucleotide, including modified nucleotides, forthe oligonucleotides tested in Table 2.

Table 5: Cell lines

DETAILED DESCRIPTION OF CERTAIN EMBODIMENTS OF THE INVENTION

Aspects of the invention provided herein relate to the discovery ofpolycomb repressive complex 2 (PRC2)-interacting RNAs. Polycombrepressive complex 2 (PRC2) is a histone methyltransferase and a knownepigenetic regulator involved in silencing of genomic regions throughmethylation of histone H3. Among other functions, PRC2 interacts withlong noncoding RNAs (lncRNAs), such as RepA, Xist, and Tsix, to catalyzetrimethylation of histone H3-lysine-27. PRC2 contains four subunits,Eed, Suz12, RbAp48, and Ezh2. Aspects of the invention relate to therecognition that single stranded oligonucleotides that bind toPRC2-associated regions of RNAs (e.g., lncRNAs) that are expressed fromwithin a genomic region that encompasses or that is in functionalproximity to the UTRN gene can induce or enhance expression of UTRN. Insome embodiments, this upregulation is believed to result frominhibition of PRC2 mediated repression of UTRN.

As used herein, the term “PRC2-associated region” refers to a region ofa nucleic acid that comprises or encodes a sequence of nucleotides thatinteract directly or indirectly with a component of PRC2. APRC2-associated region may be present in a RNA (e.g., a long non-codingRNA (lncRNA)) that that interacts with a PRC2. A PRC2-associated regionmay be present in a DNA that encodes an RNA that interacts with PRC2. Insome cases, the PRC2-associated region is equivalently referred to as aPRC2-interacting region.

In some embodiments, a PRC2-associated region is a region of an RNA thatcrosslinks to a component of PRC2 in response to in situ ultravioletirradiation of a cell that expresses the RNA, or a region of genomic DNAthat encodes that RNA region. In some embodiments, a PRC2-associatedregion is a region of an RNA that immunoprecipitates with an antibodythat targets a component of PRC2, or a region of genomic DNA thatencodes that RNA region. In some embodiments, a PRC2-associated regionis a region of an RNA that immunoprecipitates with an antibody thatbinds specifically to SUZ12, EED, EZH2 or RBBP4 (which as noted aboveare components of PRC2), or a region of genomic DNA that encodes thatRNA region.

In some embodiments, a PRC2-associated region is a region of an RNA thatis protected from nucleases (e.g., RNases) in an RNA-immunoprecipitationassay that employs an antibody that targets a component of PRC2, or aregion of genomic DNA that encodes that protected RNA region. In someembodiments, a PRC2-associated region is a region of an RNA that isprotected from nucleases (e.g., RNases) in an RNA-immunoprecipitationassay that employs an antibody that targets SUZ12, EED, EZH2 or RBBP4,or a region of genomic DNA that encodes that protected RNA region.

In some embodiments, a PRC2-associated region is a region of an RNAwithin which occur a relatively high frequency of sequence reads in asequencing reaction of products of an RNA-immunoprecipitation assay thatemploys an antibody that targets a component of PRC2, or a region ofgenomic DNA that encodes that RNA region. In some embodiments, aPRC2-associated region is a region of an RNA within which occur arelatively high frequency of sequence reads in a sequencing reaction ofproducts of an RNA-immunoprecipitation assay that employs an antibodythat binds specifically to SUZ12, EED, EZH2 or RBBP4, or a region ofgenomic DNA that encodes that protected RNA region. In such embodiments,the PRC2-associated region may be referred to as a “peak.”

In some embodiments, a PRC2-associated region comprises a sequence of 40to 60 nucleotides that interact with PRC2 complex. In some embodiments,a PRC2-associated region comprises a sequence of 40 to 60 nucleotidesthat encode an RNA that interacts with PRC2. In some embodiments, aPRC2-associated region comprises a sequence of up to 5 kb in length thatcomprises a sequence (e.g., of 40 to 60 nucleotides) that interacts withPRC2. In some embodiments, a PRC2-associated region comprises a sequenceof up to 5 kb in length within which an RNA is encoded that has asequence (e.g., of 40 to 60 nucleotides) that is known to interact withPRC2. In some embodiments, a PRC2-associated region comprises a sequenceof about 4 kb in length that comprise a sequence (e.g., of 40 to 60nucleotides) that interacts with PRC2. In some embodiments, aPRC2-associated region comprises a sequence of about 4 kb in lengthwithin which an RNA is encoded that includes a sequence (e.g., of 40 to60 nucleotides) that is known to interact with PRC2. In someembodiments, a PRC2-associated region has a sequence as set forth in anyone of SEQ ID NOS: 5 to 462.

In some embodiments, single stranded oligonucleotides are provided thatspecifically bind to, or are complementary to, a PRC2-associated regionin a genomic region that encompasses or that is in proximity to the UTRNgene. In some embodiments, single stranded oligonucleotides are providedthat specifically bind to, or are complementary to, a PRC2-associatedregion that has a sequence as set forth in any one of SEQ ID NOS: 5 to462. In some embodiments, single stranded oligonucleotides are providedthat specifically bind to, or are complementary to, a PRC2-associatedregion that has a sequence as set forth in any one of SEQ ID NOS: 4 to462 combined with up to 2 kb, up to 5 kb, or up to 10 kb of flankingsequences from a corresponding genomic region to which these SEQ IDs map(e.g., in a human genome). In some embodiments, single strandedoligonucleotides have a sequence as set forth in any one of SEQ ID NOS:463 to 497728. In some embodiments, single stranded oligonucleotideshave a sequence as set forth in Table 4.

Without being bound by a theory of invention, these oligonucleotides areable to interfere with the binding of and function of PRC2, bypreventing recruitment of PRC2 to a specific chromosomal locus. Forexample, a single administration of single stranded oligonucleotidesdesigned to specifically bind a PRC2-associated region lncRNA can stablydisplace not only the lncRNA, but also the PRC2 that binds to thelncRNA, from binding chromatin. After displacement, the full complementof PRC2 is not recovered for up to 24 hours. Further, lncRNA can recruitPRC2 in a cis fashion, repressing gene expression at or near thespecific chromosomal locus from which the lncRNA was transcribed.

Methods of modulating gene expression are provided, in some embodiments,that may be carried out in vitro, ex vivo, or in vivo. It is understoodthat any reference to uses of compounds throughout the descriptioncontemplates use of the compound in preparation of a pharmaceuticalcomposition or medicament for use in the treatment of musculardystrophies, including DMD, BMD, and myotonic dystrophy. Thus, as onenonlimiting example, this aspect of the invention includes use of suchsingle stranded oligonucleotides in the preparation of a medicament foruse in the treatment of disease, wherein the treatment involvesupregulating expression of UTRN.

In further aspects of the invention, methods are provided for selectinga candidate oligonucleotide for activating expression of UTRN. Themethods generally involve selecting as a candidate oligonucleotide, asingle stranded oligonucleotide comprising a nucleotide sequence that iscomplementary to a PRC2-associated region (e.g., a nucleotide sequenceas set forth in any one of SEQ ID NOS: 5 to 462). In some embodiments,sets of oligonucleotides may be selected that are enriched (e.g.,compared with a random selection of oligonucleotides) inoligonucleotides that activate expression of UTRN.

Single Stranded Oligonucleotides for Modulating Expression of UTRN

In one aspect of the invention, single stranded oligonucleotidescomplementary to the PRC2-associated regions are provided for modulatingexpression of UTRN in a cell. In some embodiments, expression of UTRN isupregulated or increased. In some embodiments, single strandedoligonucleotides complementary to these PRC2-associated regions inhibitthe interaction of PRC2 with long RNA transcripts such that geneexpression is upregulated or increased. In some embodiments, singlestranded oligonucleotides complementary to these PRC2-associated regionsinhibit the interaction of PRC2 with long RNA transcripts, resulting inreduced methylation of histone H3 and reduced gene inactivation, suchthat gene expression is upregulated or increased. In some embodiments,this interaction may be disrupted or inhibited due to a change in thestructure of the long RNA that prevents or reduces binding to PRC2. Theoligonucleotide may be selected using any of the methods disclosedherein for selecting a candidate oligonucleotide for activatingexpression of UTRN.

The single stranded oligonucleotide may comprise a region ofcomplementarity that is complementary with a PRC2-associated region of anucleotide sequence set forth in any one of SEQ ID NOS: 1 to 4. Theregion of complementarity of the single stranded oligonucleotide may becomplementary with at least 6, e.g., at least 7, at least 8, at least 9,at least 10, at least 15 or more consecutive nucleotides of thePRC2-associated region.

The PRC2-associated region may map to a position in a chromosome between50 kilobases upstream of a 5′-end of the UTRN gene and 50 kilobasesdownstream of a 3′-end of the UTRN gene. The PRC2-associated region maymap to a position in a chromosome between 25 kilobases upstream of a5′-end of the UTRN gene and 25 kilobases downstream of a 3′-end of theUTRN gene. The PRC2-associated region may map to a position in achromosome between 12 kilobases upstream of a 5′-end of the UTRN geneand 12 kilobases downstream of a 3′-end of the UTRN gene. ThePRC2-associated region may map to a position in a chromosome between 5kilobases upstream of a 5′-end of the UTRN gene and 5 kilobasesdownstream of a 3′-end of the UTRN gene.

The genomic position of the selected PRC2-associated region relative tothe UTRN gene may vary. For example, the PRC2-associated region may beupstream of the 5′ end of the UTRN gene. The PRC2-associated region maybe downstream of the 3′ end of the UTRN gene. The PRC2-associated regionmay be within an intron of the UTRN gene. The PRC2-associated region maybe within an exon of the UTRN gene. The PRC2-associated region maytraverse an intron-exon junction, a 5′-UTR-exon junction or a3′-UTR-exon junction of the UTRN gene.

The single stranded oligonucleotide may comprise a sequence having theformula X-Y-Z, in which X is any nucleotide, Y is a nucleotide sequenceof 6 nucleotides in length that is not a human seed sequence of amicroRNA, and Z is a nucleotide sequence of varying length. In someembodiments X is the 5′ nucleotide of the oligonucleotide. In someembodiments, when X is anchored at the 5′ end of the oligonucleotide,the oligonucleotide does not have any nucleotides or nucleotide analogslinked 5′ to X. In some embodiments, other compounds such as peptides orsterols may be linked at the 5′ end in this embodiment as long as theyare not nucleotides or nucleotide analogs. In some embodiments, thesingle stranded oligonucleotide has a sequence 5′X-Y-Z and is 8-50nucleotides in length. Oligonucleotides that have these sequencecharacteristics are predicted to avoid the miRNA pathway. Therefore, insome embodiments, oligonucleotides having these sequence characteristicsare unlikely to have an unintended consequence of functioning in a cellas a miRNA molecule. The Y sequence may be a nucleotide sequence of 6nucleotides in length set forth in Table 1.

The single stranded oligonucleotide may have a sequence that does notcontain guanosine nucleotide stretches (e.g., 3 or more, 4 or more, 5 ormore, 6 or more consecutive guanosine nucleotides). In some embodiments,oligonucleotides having guanosine nucleotide stretches have increasednon-specific binding and/or off-target effects, compared witholigonucleotides that do not have guanosine nucleotide stretches.

The single stranded oligonucleotide may have a sequence that has lessthan a threshold level of sequence identity with every sequence ofnucleotides, of equivalent length, that map to a genomic positionencompassing or in proximity to an off-target gene. For example, anoligonucleotide may be designed to ensure that it does not have asequence that maps to genomic positions encompassing or in proximitywith all known genes (e.g., all known protein coding genes) other thanUTRN. In a similar embodiment, an oligonucleotide may be designed toensure that it does not have a sequence that maps to any other knownPRC2-associated region, particularly PRC2-associated regions that arefunctionally related to any other known gene (e.g., any other knownprotein coding gene). In either case, the oligonucleotide is expected tohave a reduced likelihood of having off-target effects. The thresholdlevel of sequence identity may be 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%or 100% sequence identity.

The single stranded oligonucleotide may have a sequence that iscomplementary to a PRC2-associated region that encodes an RNA that formsa secondary structure comprising at least two single stranded loops. Inhas been discovered that, in some embodiments, oligonucleotides that arecomplementary to a PRC2-associated region that encodes an RNA that formsa secondary structure comprising one or more single stranded loops(e.g., at least two single stranded loops) have a greater likelihood ofbeing active (e.g., of being capable of activating or enhancingexpression of a target gene) than a randomly selected oligonucleotide.In some cases, the secondary structure may comprise a double strandedstem between the at least two single stranded loops. Accordingly, theregion of complementarity between the oligonucleotide and thePRC2-associated region may be at a location of the PRC2 associatedregion that encodes at least a portion of at least one of the loops. Insome cases, the region of complementarity between the oligonucleotideand the PRC2-associated region may be at a location of thePRC2-associated region that encodes at least a portion of at least twoof the loops. In some cases, the region of complementarity between theoligonucleotide and the PRC2-associated region may be at a location ofthe PRC2 associated region that encodes at least a portion of the doublestranded stem. In some embodiments, a PRC2-associated region (e.g., ofan lncRNA) is identified (e.g., using RIP-Seq methodology or informationderived therefrom). In some embodiments, the predicted secondarystructure RNA (e.g., lncRNA) containing the PRC2-associated region isdetermined using RNA secondary structure prediction algorithms, e.g.,RNAfold, mfold. In some embodiments, oligonucleotides are designed totarget a region of the RNA that forms a secondary structure comprisingone or more single stranded loop (e.g., at least two single strandedloops) structures which may comprise a double stranded stem between theat least two single stranded loops.

The single stranded oligonucleotide may have a sequence that is hasgreater than 30% G-C content, greater than 40% G-C content, greater than50% G-C content, greater than 60% G-C content, greater than 70% G-Ccontent, or greater than 80% G-C content. The single strandedoligonucleotide may have a sequence that has up to 100% G-C content, upto 95% G-C content, up to 90% G-C content, or up to 80% G-C content. Insome embodiments in which the oligonucleotide is 8 to 10 nucleotides inlength, all but 1, 2, 3, 4, or 5 of the nucleotides of the complementarysequence of the PRC2-associated region are cytosine or guanosinenucleotides. In some embodiments, the sequence of the PRC2-associatedregion to which the single stranded oligonucleotide is complementarycomprises no more than 3 nucleotides selected from adenine and uracil.

The single stranded oligonucleotide may be complementary to a chromosomeof a different species (e.g., a mouse, rat, rabbit, goat, monkey, etc.)at a position that encompasses or that is in proximity to that species'homolog of UTRN. The single stranded oligonucleotide may becomplementary to a human genomic region encompassing or in proximity tothe UTRN gene and also be complementary to a mouse genomic regionencompassing or in proximity to the mouse homolog of UTRN. For example,the single stranded oligonucleotide may be complementary to a sequenceas set forth in SEQ ID NO: 1 or 2, which is a human genomic regionencompassing or in proximity to the UTRN gene, and also be complementaryto a sequence as set forth in SEQ ID NO: 3 or 4, which is a mousegenomic region encompassing or in proximity to the mouse homolog of theUTRN gene. Oligonucleotides having these characteristics may be testedin vivo or in vitro for efficacy in multiple species (e.g., human andmouse). This approach also facilitates development of clinicalcandidates for treating human disease by selecting a species in which anappropriate animal exists for the disease.

In some embodiments, the region of complementarity of the singlestranded oligonucleotide is complementary with at least 8 to 15, 8 to30, 8 to 40, or 10 to 50, or 5 to 50, or 5 to 40 bases, e.g., 5, 6, 7,8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25,26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43,44, 45, 46, 47, 48, 49, or 50 consecutive nucleotides of aPRC2-associated region. In some embodiments, the region ofcomplementarity is complementary with at least 8 consecutive nucleotidesof a PRC2-associated region. In some embodiments the sequence of thesingle stranded oligonucleotide is based on an RNA sequence that bindsto PRC2, or a portion thereof, said portion having a length of from 5 to40 contiguous base pairs, or about 8 to 40 bases, or about 5 to 15, orabout 5 to 30, or about 5 to 40 bases, or about 5 to 50 bases.

Complementary, as the term is used in the art, refers to the capacityfor precise pairing between two nucleotides. For example, if anucleotide at a certain position of an oligonucleotide is capable ofhydrogen bonding with a nucleotide at the same position ofPRC2-associated region, then the single stranded nucleotide andPRC2-associated region are considered to be complementary to each otherat that position. The single stranded nucleotide and PRC2-associatedregion are complementary to each other when a sufficient number ofcorresponding positions in each molecule are occupied by nucleotidesthat can hydrogen bond with each other through their bases. Thus,“complementary” is a term which is used to indicate a sufficient degreeof complementarity or precise pairing such that stable and specificbinding occurs between the single stranded nucleotide andPRC2-associated region. For example, if a base at one position of asingle stranded nucleotide is capable of hydrogen bonding with a base atthe corresponding position of a PRC2-associated region, then the basesare considered to be complementary to each other at that position. 100%complementarity is not required.

The single stranded oligonucleotide may be at least 80% complementary to(optionally one of at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%,98%, 99% or 100% complementary to) the consecutive nucleotides of aPRC2-associated region. In some embodiments the single strandedoligonucleotide may contain 1, 2 or 3 base mismatches compared to theportion of the consecutive nucleotides of a PRC2-associated region. Insome embodiments the single stranded oligonucleotide may have up to 3mismatches over 15 bases, or up to 2 mismatches over 10 bases.

It is understood in the art that a complementary nucleotide sequenceneed not be 100% complementary to that of its target to be specificallyhybridizable. In some embodiments, a complementary nucleic acid sequencefor purposes of the present disclosure is specifically hybridizable whenbinding of the sequence to the target molecule (e.g., lncRNA) interfereswith the normal function of the target (e.g., lncRNA) to cause a loss ofactivity (e.g., inhibiting PRC2-associated repression with consequentup-regulation of gene expression) and there is a sufficient degree ofcomplementarity to avoid non-specific binding of the sequence tonon-target sequences under conditions in which avoidance of non-specificbinding is desired, e.g., under physiological conditions in the case ofin vivo assays or therapeutic treatment, and in the case of in vitroassays, under conditions in which the assays are performed undersuitable conditions of stringency.

In some embodiments, the single stranded oligonucleotide is 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28,29, 30, 35, 40, 45, 50 or more nucleotides in length. In a preferredembodiment, the oligonucleotide is 8 to 30 nucleotides in length.

In some embodiments, the PRC2-associated region occurs on the same DNAstrand as a gene sequence (sense). In some embodiments, thePRC2-associated region occurs on the opposite DNA strand as a genesequence (anti-sense). Oligonucleotides complementary to aPRC2-associated region can bind either sense or anti-sense sequences.Base pairings may include both canonical Watson-Crick base pairing andnon-Watson-Crick base pairing (e.g., Wobble base pairing and Hoogsteenbase pairing). It is understood that for complementary base pairings,adenosine-type bases (A) are complementary to thymidine-type bases (T)or uracil-type bases (U), that cytosine-type bases (C) are complementaryto guanosine-type bases (G), and that universal bases such as3-nitropyrrole or 5-nitroindole can hybridize to and are consideredcomplementary to any A, C, U, or T. Inosine (I) has also been consideredin the art to be a universal base and is considered complementary to anyA, C, U or T.

In some embodiments, any one or more thymidine (T) nucleotides (ormodified nucleotide thereof) or uridine (U) nucleotides (or a modifiednucleotide thereof) in a sequence provided herein, including a sequenceprovided in the sequence listing, may be replaced with any othernucleotide suitable for base pairing (e.g., via a Watson-Crick basepair) with an adenosine nucleotide. In some embodiments, any one or morethymidine (T) nucleotides (or modified nucleotide thereof) or uridine(U) nucleotides (or a modified nucleotide thereof) in a sequenceprovided herein, including a sequence provided in the sequence listing,may be suitably replaced with a different pyrimidine nucleotide or viceversa. In some embodiments, any one or more thymidine (T) nucleotides(or modified nucleotide thereof) in a sequence provided herein,including a sequence provided in the sequence listing, may be suitablyreplaced with a uridine (U) nucleotide (or a modified nucleotidethereof) or vice versa.

In some embodiments, GC content of the single stranded oligonucleotideis preferably between about 30-60%. Contiguous runs of three or more Gsor Cs may not be preferable in some embodiments. Accordingly, in someembodiments, the oligonucleotide does not comprise a stretch of three ormore guanosine nucleotides.

In some embodiments, the single stranded oligonucleotide specificallybinds to, or is complementary to an RNA that is encoded in a genome(e.g., a human genome) as a single contiguous transcript (e.g., as anon-spliced RNA). In some embodiments, the single strandedoligonucleotide specifically binds to, or is complementary to an RNAthat is encoded in a genome (e.g., a human genome), in which thedistance in the genome between the 5′ end of the coding region of theRNA and the 3′ end of the coding region of the RNA is less than 1 kb,less than 2 kb, less than 3 kb, less than 4 kb, less than 5 kb, lessthan 7 kb, less than 8 kb, less than 9 kb, less than 10 kb, or less than20 kb.

It is to be understood that any oligonucleotide provided herein can beexcluded. In some embodiments, a single stranded oligonucleotide is notcomplementary to SEQ ID NO: 497807.

In some embodiments, a single-stranded oligonucleotide is complementaryto a sequence within nucleotides 1 to 2897 or 2931 to 4046 of SEQ ID NO:272. In some embodiments, a single-stranded oligonucleotide iscomplementary to a sequence within nucleotides 1 to 2737 or 3137 to 4024of SEQ ID NO: 399.

In some embodiments, it has been found that single strandedoligonucleotides disclosed herein may increase expression of mRNAcorresponding to the gene by at least about 50% (i.e. 150% of normal or1.5 fold), or by about 2 fold to about 5 fold. In some embodiments,expression may be increased by at least about 15 fold, 20 fold, 30 fold,40 fold, 50 fold or 100 fold, or any range between any of the foregoingnumbers. It has also been found that increased mRNA expression has beenshown to correlate to increased protein expression.

In some or any of the embodiments of the oligonucleotides describedherein, or processes for designing or synthesizing them, theoligonucleotides will upregulate gene expression and may specificallybind or specifically hybridize or be complementary to the PRC2 bindingRNA that is transcribed from the same strand as a protein codingreference gene. The oligonucleotide may bind to a region of the PRC2binding RNA that originates within or overlaps an intron, exon, intronexon junction, 5′ UTR, 3′ UTR, a translation initiation region, or atranslation termination region of a protein coding sense strand of areference gene (refGene).

In some or any of the embodiments of oligonucleotides described herein,or processes for designing or synthesizing them, the oligonucleotideswill upregulate gene expression and may specifically bind orspecifically hybridize or be complementary to a PRC2 binding RNA thattranscribed from the opposite strand (the antisense strand) of a proteincoding reference gene. The oligonucleotide may bind to a region of thePRC2 binding RNA that originates within or overlaps an intron, exon,intron exon junction, 5′ UTR, 3′ UTR, a translation initiation region,or a translation termination region of a protein coding antisense strandof a reference gene

The oligonucleotides described herein may be modified, e.g., comprise amodified sugar moiety, a modified internucleoside linkage, a modifiednucleotide and/or combinations thereof. In addition, theoligonucleotides can exhibit one or more of the following properties: donot induce substantial cleavage or degradation of the target RNA; do notcause substantially complete cleavage or degradation of the target RNA;do not activate the RNAse H pathway; do not activate RISC; do notrecruit any Argonaute family protein; are not cleaved by Dicer; do notmediate alternative splicing; are not immune stimulatory; are nucleaseresistant; have improved cell uptake compared to unmodifiedoligonucleotides; are not toxic to cells or mammals; may have improvedendosomal exit; do interfere with interaction of lncRNA with PRC2,preferably the Ezh2 subunit but optionally the Suz12, Eed, RbAp46/48subunits or accessory factors such as Jarid2; do decrease histone H3lysine-27 methylation and/or do upregulate gene expression.

Oligonucleotides that are designed to interact with RNA to modulate geneexpression are a distinct subset of base sequences from those that aredesigned to bind a DNA target (e.g., are complementary to the underlyinggenomic DNA sequence from which the RNA is transcribed).

Any of the oligonucleotides disclosed herein may be linked to one ormore other oligonucleotides disclosed herein by a linker, e.g., acleavable linker.

Method for Selecting Candidate Oligonucleotides for ActivatingExpression of UTRN

Methods are provided herein for selecting a candidate oligonucleotidefor activating or enhancing expression of UTRN. The target selectionmethods may generally involve steps for selecting single strandedoligonucleotides having any of the structural and functionalcharacteristics disclosed herein. Typically, the methods involve one ormore steps aimed at identifying oligonucleotides that target aPRC2-associated region that is functionally related to UTRN, for examplea PRC2-associated region of a lncRNA that regulates expression of UTRNby facilitating (e.g., in a cis-regulatory manner) the recruitment ofPRC2 to the UTRN gene. Such oligonucleotides are expected to becandidates for activating expression of UTRN because of their ability tohybridize with the PRC2-associated region of a nucleic acid (e.g., alncRNA). In some embodiments, this hybridization event is understood todisrupt interaction of PRC2 with the nucleic acid (e.g., a lncRNA) andas a result disrupt recruitment of PRC2 and its associated co-repressors(e.g., chromatin remodeling factors) to the UTRN gene locus.

Methods of selecting a candidate oligonucleotide may involve selecting aPRC2-associated region (e.g., a nucleotide sequence as set forth in anyone of SEQ ID NOS: 5 to 462) that maps to a chromosomal positionencompassing or in proximity to the UTRN gene (e.g., a chromosomalposition having a sequence as set forth in any one of SEQ ID NOS: 1 to4). The PRC2-associated region may map to the strand of the chromosomecomprising the sense strand of the UTRN gene, in which case thecandidate oligonucleotide is complementary to the sense strand of theUTRN gene (i.e., is antisense to the UTRN gene). Alternatively, thePRC2-associated region may map to the strand of the first chromosomecomprising the antisense strand of the UTRN gene, in which case theoligonucleotide is complementary to the antisense strand (the templatestrand) of the UTRN gene (i.e., is sense to the UTRN gene).

Methods for selecting a set of candidate oligonucleotides that isenriched in oligonucleotides that activate expression of UTRN mayinvolve selecting one or more PRC2-associated regions that map to achromosomal position that encompasses or that is in proximity to theUTRN gene and selecting a set of oligonucleotides, in which eacholigonucleotide in the set comprises a nucleotide sequence that iscomplementary with the one or more PRC2-associated regions. As usedherein, the phrase, “a set of oligonucleotides that is enriched inoligonucleotides that activate expression of” refers to a set ofoligonucleotides that has a greater number of oligonucleotides thatactivate expression of a target gene (e.g., UTRN) compared with a randomselection of oligonucleotides of the same physicochemical properties(e.g., the same GC content, T_(m), length etc.) as the enriched set.

Where the design and/or synthesis of a single stranded oligonucleotideinvolves design and/or synthesis of a sequence that is complementary toa nucleic acid or PRC2-associated region described by such sequenceinformation, the skilled person is readily able to determine thecomplementary sequence, e.g., through understanding of Watson Crick basepairing rules which form part of the common general knowledge in thefield.

In some embodiments design and/or synthesis of a single strandedoligonucleotide involves manufacture of an oligonucleotide from startingmaterials by techniques known to those of skill in the art, where thesynthesis may be based on a sequence of a PRC2-associated region, orportion thereof.

Methods of design and/or synthesis of a single stranded oligonucleotidemay involve one or more of the steps of:

Identifying and/or selecting PRC2-associated region;

Designing a nucleic acid sequence having a desired degree of sequenceidentity or complementarity to a PRC2-associated region or a portionthereof;

Synthesizing a single stranded oligonucleotide to the designed sequence;

Purifying the synthesized single stranded oligonucleotide; and

Optionally mixing the synthesized single stranded oligonucleotide withat least one pharmaceutically acceptable diluent, carrier or excipientto form a pharmaceutical composition or medicament.

Single stranded oligonucleotides so designed and/or synthesized may beuseful in method of modulating gene expression as described herein.

Preferably, single stranded oligonucleotides of the invention aresynthesized chemically. Oligonucleotides used to practice this inventioncan be synthesized in vitro by well-known chemical synthesis techniques.

Oligonucleotides of the invention can be stabilized against nucleolyticdegradation such as by the incorporation of a modification, e.g., anucleotide modification. For example, nucleic acid sequences of theinvention include a phosphorothioate at least the first, second, orthird internucleotide linkage at the 5′ or 3′ end of the nucleotidesequence. As another example, the nucleic acid sequence can include a2′-modified nucleotide, e.g., a 2′-deoxy, 2′-deoxy-2′-fluoro,2′-O-methyl, 2′-O-methoxyethyl (2′-O-MOE), 2′-O-aminopropyl (2′-O-AP),2′-O-dimethylaminoethyl (2′-O-DMAOE), 2′-O-dimethylaminopropyl(2′-O-DMAP), 2′-O-dimethylaminoethyloxyethyl (2′-O-DMAEOE), or2′-O—N-methylacetamido (2′-O-NMA). As another example, the nucleic acidsequence can include at least one 2′-O-methyl-modified nucleotide, andin some embodiments, all of the nucleotides include a 2′-O-methylmodification. In some embodiments, the nucleic acids are “locked,” i.e.,comprise nucleic acid analogues in which the ribose ring is “locked” bya methylene bridge connecting the 2′-O atom and the 4′-C atom.

It is understood that any of the modified chemistries or formats ofsingle stranded oligonucleotides described herein can be combined witheach other, and that one, two, three, four, five, or more differenttypes of modifications can be included within the same molecule.

In some embodiments, the method may further comprise the steps ofamplifying the synthesized single stranded oligonucleotide, and/orpurifying the single stranded oligonucleotide (or amplified singlestranded oligonucleotide), and/or sequencing the single strandedoligonucleotide so obtained.

As such, the process of preparing a single stranded oligonucleotide maybe a process that is for use in the manufacture of a pharmaceuticalcomposition or medicament for use in the treatment of disease,optionally wherein the treatment involves modulating expression of agene associated with a PRC2-associated region.

In the methods described above a PRC2-associated region may be, or havebeen, identified, or obtained, by a method that involves identifying RNAthat binds to PRC2.

Such methods may involve the following steps: providing a samplecontaining nuclear ribonucleic acids, contacting the sample with anagent that binds specifically to PRC2 or a subunit thereof, allowingcomplexes to form between the agent and protein in the sample,partitioning the complexes, synthesizing nucleic acid that iscomplementary to nucleic acid present in the complexes.

Where the single stranded oligonucleotide is based on a PRC2-associatedregion, or a portion of such a sequence, it may be based on informationabout that sequence, e.g., sequence information available in written orelectronic form, which may include sequence information contained inpublicly available scientific publications or sequence databases.

Nucleotide Analogues

In some embodiments, the oligonucleotide may comprise at least oneribonucleotide, at least one deoxyribonucleotide, and/or at least onebridged nucleotide. In some embodiments, the oligonucleotide maycomprise a bridged nucleotide, such as a locked nucleic acid (LNA)nucleotide, a constrained ethyl (cEt) nucleotide, or an ethylene bridgednucleic acid (ENA) nucleotide. Examples of such nucleotides aredisclosed herein and known in the art. In some embodiments, theoligonucleotide comprises a nucleotide analog disclosed in one of thefollowing United States patent or patent application Publications: U.S.Pat. No. 7,399,845, U.S. Pat. No. 7,741,457, U.S. Pat. No. 8,022,193,U.S. Pat. No. 7,569,686, U.S. Pat. No. 7,335,765, U.S. Pat. No.7,314,923, U.S. Pat. No. 7,335,765, and U.S. Pat. No. 7,816,333, US20110009471, the entire contents of each of which are incorporatedherein by reference for all purposes. The oligonucleotide may have oneor more 2′ O-methyl nucleotides. The oligonucleotide may consistentirely of 2′ O-methyl nucleotides.

Often the single stranded oligonucleotide has one or more nucleotideanalogues. For example, the single stranded oligonucleotide may have atleast one nucleotide analogue that results in an increase in T_(m) ofthe oligonucleotide in a range of 1° C., 2° C., 3° C., 4° C., or 5° C.compared with an oligonucleotide that does not have the at least onenucleotide analogue. The single stranded oligonucleotide may have aplurality of nucleotide analogues that results in a total increase inT_(m) of the oligonucleotide in a range of 2° C., 3° C., 4° C., 5° C.,6° C., 7° C., 8° C., 9° C., 10° C., 15° C., 20° C., 25° C., 30° C., 35°C., 40° C., 45° C. or more compared with an oligonucleotide that doesnot have the nucleotide analogue.

The oligonucleotide may be of up to 50 nucleotides in length in which 2to 10, 2 to 15, 2 to 16, 2 to 17, 2 to 18, 2 to 19, 2 to 20, 2 to 25, 2to 30, 2 to 40, 2 to 45, or more nucleotides of the oligonucleotide arenucleotide analogues. The oligonucleotide may be of 8 to 30 nucleotidesin length in which 2 to 10, 2 to 15, 2 to 16, 2 to 17, 2 to 18, 2 to 19,2 to 20, 2 to 25, 2 to 30 nucleotides of the oligonucleotide arenucleotide analogues.

The oligonucleotide may be of 8 to 15 nucleotides in length in which 2to 4, 2 to 5, 2 to 6, 2 to 7, 2 to 8, 2 to 9, 2 to 10, 2 to 11, 2 to 12,2 to 13, 2 to 14 nucleotides of the oligonucleotide are nucleotideanalogues. Optionally, the oligonucleotides may have every nucleotideexcept 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 nucleotides modified.

The oligonucleotide may consist entirely of bridged nucleotides (e.g.,LNA nucleotides, cEt nucleotides, ENA nucleotides). The oligonucleotidemay comprise alternating deoxyribonucleotides and2′-fluoro-deoxyribonucleotides. The oligonucleotide may comprisealternating deoxyribonucleotides and 2′-O-methyl nucleotides. Theoligonucleotide may comprise alternating deoxyribonucleotides and ENAnucleotide analogues. The oligonucleotide may comprise alternatingdeoxyribonucleotides and LNA nucleotides. The oligonucleotide maycomprise alternating LNA nucleotides and 2′-O-methyl nucleotides. Theoligonucleotide may have a 5′ nucleotide that is a bridged nucleotide(e.g., a LNA nucleotide, cEt nucleotide, ENA nucleotide). Theoligonucleotide may have a 5′ nucleotide that is a deoxyribonucleotide.

The oligonucleotide may comprise deoxyribonucleotides flanked by atleast one bridged nucleotide (e.g., a LNA nucleotide, cEt nucleotide,ENA nucleotide) on each of the 5′ and 3′ ends of thedeoxyribonucleotides. The oligonucleotide may comprisedeoxyribonucleotides flanked by 1, 2, 3, 4, 5, 6, 7, 8 or more bridgednucleotides (e.g., LNA nucleotides, cEt nucleotides, ENA nucleotides) oneach of the 5′ and 3′ ends of the deoxyribonucleotides. The 3′ positionof the oligonucleotide may have a 3′ hydroxyl group. The 3′ position ofthe oligonucleotide may have a 3′ thiophosphate.

The oligonucleotide may be conjugated with a label. For example, theoligonucleotide may be conjugated with a biotin moiety, cholesterol,Vitamin A, folate, sigma receptor ligands, aptamers, peptides, such asCPP, hydrophobic molecules, such as lipids, ASGPR or dynamicpolyconjugates and variants thereof at its 5′ or 3′ end.

Preferably the single stranded oligonucleotide comprises one or moremodifications comprising: a modified sugar moiety, and/or a modifiedinternucleoside linkage, and/or a modified nucleotide and/orcombinations thereof. It is not necessary for all positions in a givenoligonucleotide to be uniformly modified, and in fact more than one ofthe modifications described herein may be incorporated in a singleoligonucleotide or even at within a single nucleoside within anoligonucleotide.

In some embodiments, the single stranded oligonucleotides are chimericoligonucleotides that contain two or more chemically distinct regions,each made up of at least one nucleotide. These oligonucleotidestypically contain at least one region of modified nucleotides thatconfers one or more beneficial properties (such as, for example,increased nuclease resistance, increased uptake into cells, increasedbinding affinity for the target) and a region that is a substrate forenzymes capable of cleaving RNA:DNA or RNA:RNA hybrids. Chimeric singlestranded oligonucleotides of the invention may be formed as compositestructures of two or more oligonucleotides, modified oligonucleotides,oligonucleosides and/or oligonucleotide mimetics as described above.Such compounds have also been referred to in the art as hybrids orgapmers. Representative United States patents that teach the preparationof such hybrid structures comprise, but are not limited to, U.S. Pat.Nos. 5,013,830; 5,149,797; 5,220,007; 5,256,775; 5,366,878; 5,403,711;5,491,133; 5,565,350; 5,623,065; 5,652,355; 5,652,356; and 5,700,922,each of which is herein incorporated by reference.

In some embodiments, the single stranded oligonucleotide comprises atleast one nucleotide modified at the 2′ position of the sugar, mostpreferably a 2′-O-alkyl, 2′-O-alkyl-O-alkyl or 2′-fluoro-modifiednucleotide. In other preferred embodiments, RNA modifications include2′-fluoro, 2′-amino and 2′ O-methyl modifications on the ribose ofpyrimidines, abasic residues or an inverted base at the 3′ end of theRNA. Such modifications are routinely incorporated into oligonucleotidesand these oligonucleotides have been shown to have a higher Tm (i.e.,higher target binding affinity) than 2′-deoxyoligonucleotides against agiven target.

A number of nucleotide and nucleoside modifications have been shown tomake the oligonucleotide into which they are incorporated more resistantto nuclease digestion than the native oligodeoxynucleotide; thesemodified oligos survive intact for a longer time than unmodifiedoligonucleotides. Specific examples of modified oligonucleotides includethose comprising modified backbones, for example, phosphorothioates,phosphotriesters, methyl phosphonates, short chain alkyl or cycloalkylintersugar linkages or short chain heteroatomic or heterocyclicintersugar linkages. Most preferred are oligonucleotides withphosphorothioate backbones and those with heteroatom backbones,particularly CH₂—NH—O—CH₂, CH, ˜N(CH₃)˜O˜CH₂ (known as amethylene(methylimino) or MMI backbone, CH₂—O—N(CH₃)—CH₂,CH₂—N(CH₃)—N(CH₃)—CH₂ and O—N(CH₃)—CH₂—CH₂ backbones, wherein the nativephosphodiester backbone is represented as O—P—O—CH,); amide backbones(see De Mesmaeker et al. Ace. Chem. Res. 1995, 28:366-374); morpholinobackbone structures (see Summerton and Weller, U.S. Pat. No. 5,034,506);peptide nucleic acid (PNA) backbone (wherein the phosphodiester backboneof the oligonucleotide is replaced with a polyamide backbone, thenucleotides being bound directly or indirectly to the aza nitrogen atomsof the polyamide backbone, see Nielsen et al., Science 1991, 254, 1497).Phosphorus-containing linkages include, but are not limited to,phosphorothioates, chiral phosphorothioates, phosphorodithioates,phosphotriesters, aminoalkylphosphotriesters, methyl and other alkylphosphonates comprising 3′alkylene phosphonates and chiral phosphonates,phosphinates, phosphoramidates comprising 3′-amino phosphoramidate andaminoalkylphosphoramidates, thionophosphoramidates,thionoalkylphosphonates, thionoalkylphosphotriesters, andboranophosphates having normal 3′-5′ linkages, 2′-5′ linked analogs ofthese, and those having inverted polarity wherein the adjacent pairs ofnucleoside units are linked 3′-5′ to 5′-3′ or 2′-5′ to 5′-2′; see U.S.Pat. Nos. 3,687,808; 4,469,863; 4,476,301; 5,023,243; 5,177,196;5,188,897; 5,264,423; 5,276,019; 5,278,302; 5,286,717; 5,321,131;5,399,676; 5,405,939; 5,453,496; 5,455,233; 5,466,677; 5,476,925;5,519,126; 5,536,821; 5,541,306; 5,550,111; 5,563,253; 5,571,799;5,587,361; and 5,625,050.

Morpholino-based oligomeric compounds are described in Dwaine A. Braaschand David R. Corey, Biochemistry, 2002, 41(14), 4503-4510); Genesis,volume 30, issue 3, 2001; Heasman, J., Dev. Biol., 2002, 243, 209-214;Nasevicius et al., Nat. Genet., 2000, 26, 216-220; Lacerra et al., Proc.Natl. Acad. Sci., 2000, 97, 9591-9596; and U.S. Pat. No. 5,034,506,issued Jul. 23, 1991. In some embodiments, the morpholino-basedoligomeric compound is a phosphorodiamidate morpholino oligomer (PMO)(e.g., as described in Iverson, Curr. Opin. Mol. Ther., 3:235-238, 2001;and Wang et al., J. Gene Med., 12:354-364, 2010; the disclosures ofwhich are incorporated herein by reference in their entireties).

Cyclohexenyl nucleic acid oligonucleotide mimetics are described in Wanget al., J. Am. Chem. Soc., 2000, 122, 8595-8602.

Modified oligonucleotide backbones that do not include a phosphorus atomtherein have backbones that are formed by short chain alkyl orcycloalkyl internucleoside linkages, mixed heteroatom and alkyl orcycloalkyl internucleoside linkages, or one or more short chainheteroatomic or heterocyclic internucleoside linkages. These comprisethose having morpholino linkages (formed in part from the sugar portionof a nucleoside); siloxane backbones; sulfide, sulfoxide and sulfonebackbones; formacetyl and thioformacetyl backbones; methylene formacetyland thioformacetyl backbones; alkene containing backbones; sulfamatebackbones; methyleneimino and methylenehydrazino backbones; sulfonateand sulfonamide backbones; amide backbones; and others having mixed N,O, S and CH2 component parts; see U.S. Pat. Nos. 5,034,506; 5,166,315;5,185,444; 5,214,134; 5,216,141; 5,235,033; 5,264,562; 5,264,564;5,405,938; 5,434,257; 5,466,677; 5,470,967; 5,489,677; 5,541,307;5,561,225; 5,596,086; 5,602,240; 5,610,289; 5,602,240; 5,608,046;5,610,289; 5,618,704; 5,623,070; 5,663,312; 5,633,360; 5,677,437; and5,677,439, each of which is herein incorporated by reference.

Modified oligonucleotides are also known that include oligonucleotidesthat are based on or constructed from arabinonucleotide or modifiedarabinonucleotide residues. Arabinonucleosides are stereoisomers ofribonucleosides, differing only in the configuration at the 2′-positionof the sugar ring. In some embodiments, a 2′-arabino modification is2′-F arabino. In some embodiments, the modified oligonucleotide is2′-fluoro-D-arabinonucleic acid (FANA) (as described in, for example,Lon et al., Biochem., 41:3457-3467, 2002 and Min et al., Bioorg. Med.Chem. Lett., 12:2651-2654, 2002; the disclosures of which areincorporated herein by reference in their entireties). Similarmodifications can also be made at other positions on the sugar,particularly the 3′ position of the sugar on a 3′ terminal nucleoside orin 2′-5′ linked oligonucleotides and the 5′ position of 5′ terminalnucleotide.

PCT Publication No. WO 99/67378 discloses arabinonucleic acids (ANA)oligomers and their analogues for improved sequence specific inhibitionof gene expression via association to complementary messenger RNA.

Other preferred modifications include ethylene-bridged nucleic acids(ENAs) (e.g., International Patent Publication No. WO 2005/042777,Morita et al., Nucleic Acid Res., Suppl 1:241-242, 2001; Surono et al.,Hum. Gene Ther., 15:749-757, 2004; Koizumi, Curr. Opin. Mol. Ther.,8:144-149, 2006 and Horie et al., Nucleic Acids Symp. Ser (Oxf),49:171-172, 2005; the disclosures of which are incorporated herein byreference in their entireties). Preferred ENAs include, but are notlimited to, 2′-O,4′-C-ethylene-bridged nucleic acids.

Examples of LNAs are described in WO/2008/043753 and include compoundsof the following general formula.

where X and Y are independently selected among the groups —O—,

—S—, —N(H)—, N(R)—, —CH₂— or —CH— (if part of a double bond),

—CH₂—O—, —CH₂—S—, —CH₂—N(H)—, —CH₂—N(R)—, —CH₂—CH₂— or —CH₂—CH— (if partof a double bond),

—CH═CH—, where R is selected from hydrogen and C₁₋₄-alkyl; Z and Z* areindependently selected among an internucleoside linkage, a terminalgroup or a protecting group; B constitutes a natural or non-naturalnucleotide base moiety; and the asymmetric groups may be found in eitherorientation.

Preferably, the LNA used in the oligonucleotides described hereincomprises at least one LNA unit according any of the formulas

wherein Y is —O—, —S—, —NH—, or N(R^(H)); Z and Z* are independentlyselected among an internucleoside linkage, a terminal group or aprotecting group; B constitutes a natural or non-natural nucleotide basemoiety, and RH is selected from hydrogen and C₁₋₄-alkyl.

In some embodiments, the Locked Nucleic Acid (LNA) used in theoligonucleotides described herein comprises at least one Locked NucleicAcid (LNA) unit according any of the formulas shown in Scheme 2 ofPCT/DK2006/000512.

In some embodiments, the LNA used in the oligomer of the inventioncomprises internucleoside linkages selected from —O—P(O)₂—O—,—O—P(O,S)—O—, —O—P(S)₂—O—, —S—P(O)₂—O—, —S—P(O,S)—O—, —S—P(S)₂—O—,—O—P(O)₂—S—, —O—P(O,S)—S—, —S—P(O)₂—S—, —O—PO(R^(H))—O—, O—PO(OCH₃)—O—,—O—PO(NR^(H))—O—, —O—PO(OCH₂CH₂S—R)—O—, —O—PO(BH₃)—O—,—O—PO(NHR^(H))—O—, —O—P(O)₂—NR^(H)—, —NR^(H)—P(O)₂—O—, —NR^(H)—CO—O—,where R^(H) is selected from hydrogen and C₁₋₄-alkyl.

Specifically preferred LNA units are shown in scheme 2:

The term “thio-LNA” comprises a locked nucleotide in which at least oneof X or Y in the general formula above is selected from S or —CH₂—S—.Thio-LNA can be in both beta-D and alpha-L-configuration.

The term “amino-LNA” comprises a locked nucleotide in which at least oneof X or Y in the general formula above is selected from —N(H)—, N(R)—,CH₂—N(H)—, and —CH₂—N(R)—where R is selected from hydrogen andC₁₋₄-alkyl. Amino-LNA can be in both beta-D and alpha-L-configuration.

The term “oxy-LNA” comprises a locked nucleotide in which at least oneof X or Y in the general formula above represents —O— or —CH₂—O—.Oxy-LNA can be in both beta-D and alpha-L-configuration.

The term “ena-LNA” comprises a locked nucleotide in which Y in thegeneral formula above is —CH₂—O— (where the oxygen atom of —CH₂—O— isattached to the 2′-position relative to the base B).

LNAs are described in additional detail herein.

One or more substituted sugar moieties can also be included, e.g., oneof the following at the 2′ position: OH, SH, SCH₃, F, OCN, OCH₃ OCH₃,OCH₃ O(CH₂)n CH₃, O(CH₂)n NH₂ or O(CH₂)n CH₃ where n is from 1 to about10; C1 to C10 lower alkyl, alkoxyalkoxy, substituted lower alkyl,alkaryl or aralkyl; Cl; Br; CN; CF₃; OCF₃; O—, S—, or N-alkyl; O—, S—,or N-alkenyl; SOCH₃; SO₂ CH₃; ONO₂; NO₂, N₃; NH2; heterocycloalkyl;heterocycloalkaryl; amino alkylamino; polyalkylamino; substituted silyl;an RNA cleaving group; a reporter group; an intercalator; a group forimproving the pharmacokinetic properties of an oligonucleotide; or agroup for improving the pharmacodynamic properties of an oligonucleotideand other substituents having similar properties. A preferredmodification includes 2′-methoxyethoxy [2′-O—CH₂CH₂OCH₃, also known as2′-O-(2-methoxyethyl)](Martin et al, Helv. Chim. Acta, 1995, 78, 486).Other preferred modifications include 2′-methoxy (2′-O—CH₃), 2′-propoxy(2′-OCH₂ CH₂CH₃) and 2′-fluoro (2′-F). Similar modifications may also bemade at other positions on the oligonucleotide, particularly the 3′position of the sugar on the 3′ terminal nucleotide and the 5′ positionof 5′ terminal nucleotide. Oligonucleotides may also have sugar mimeticssuch as cyclobutyls in place of the pentofuranosyl group.

Single stranded oligonucleotides can also include, additionally oralternatively, nucleobase (often referred to in the art simply as“base”) modifications or substitutions. As used herein, “unmodified” or“natural” nucleobases include adenine (A), guanine (G), thymine (T),cytosine (C) and uracil (U). Modified nucleobases include nucleobasesfound only infrequently or transiently in natural nucleic acids, e.g.,hypoxanthine, 6-methyladenine, 5-Me pyrimidines, particularly5-methylcytosine (also referred to as 5-methyl-2′ deoxycytosine andoften referred to in the art as 5-Me-C), 5-hydroxymethylcytosine (HMC),glycosyl HMC and gentobiosyl HMC, isocytosine, pseudoisocytosine, aswell as synthetic nucleobases, e.g., 2-aminoadenine,2-(methylamino)adenine, 2-(imidazolylalkyl)adenine,2-(aminoalklyamino)adenine or other heterosubstituted alkyladenines,2-thiouracil, 2-thiothymine, 5-bromouracil, 5-hydroxymethyluracil,5-propynyluracil, 8-azaguanine, 7-deazaguanine, N6(6-aminohexyl)adenine, 6-aminopurine, 2-aminopurine,2-chloro-6-aminopurine and 2,6-diaminopurine or other diaminopurines.See, e.g., Kornberg, “DNA Replication,” W. H. Freeman & Co., SanFrancisco, 1980, pp 75-77; and Gebeyehu, G., et al. Nucl. Acids Res.,15:4513 (1987)). A “universal” base known in the art, e.g., inosine, canalso be included. 5-Me-C substitutions have been shown to increasenucleic acid duplex stability by 0.6-1.2° C. (Sanghvi, in Crooke, andLebleu, eds., Antisense Research and Applications, CRC Press, BocaRaton, 1993, pp. 276-278) and may be used as base substitutions.

It is not necessary for all positions in a given oligonucleotide to beuniformly modified, and in fact more than one of the modificationsdescribed herein may be incorporated in a single oligonucleotide or evenat within a single nucleoside within an oligonucleotide.

In some embodiments, both a sugar and an internucleoside linkage, i.e.,the backbone, of the nucleotide units are replaced with novel groups.The base units are maintained for hybridization with an appropriatenucleic acid target compound. One such oligomeric compound, anoligonucleotide mimetic that has been shown to have excellenthybridization properties, is referred to as a peptide nucleic acid(PNA). In PNA compounds, the sugar-backbone of an oligonucleotide isreplaced with an amide containing backbone, for example, anaminoethylglycine backbone. The nucleobases are retained and are bounddirectly or indirectly to aza nitrogen atoms of the amide portion of thebackbone. Representative United States patents that teach thepreparation of PNA compounds include, but are not limited to, U.S. Pat.Nos. 5,539,082; 5,714,331; and 5,719,262, each of which is hereinincorporated by reference. Further teaching of PNA compounds can befound in Nielsen et al, Science, 1991, 254, 1497-1500.

Single stranded oligonucleotides can also include one or more nucleobase(often referred to in the art simply as “base”) modifications orsubstitutions. As used herein, “unmodified” or “natural” nucleobasescomprise the purine bases adenine (A) and guanine (G), and thepyrimidine bases thymine (T), cytosine (C) and uracil (U). Modifiednucleobases comprise other synthetic and natural nucleobases such as5-methylcytosine (5-me-C), 5-hydroxymethyl cytosine, xanthine,hypoxanthine, 2-aminoadenine, 6-methyl and other alkyl derivatives ofadenine and guanine, 2-propyl and other alkyl derivatives of adenine andguanine, 2-thiouracil, 2-thiothymine and 2-thiocytosine, 5-halouraciland cytosine, 5-propynyl uracil and cytosine, 6-azo uracil, cytosine andthymine, 5-uracil (pseudo-uracil), 4-thiouracil, 8-halo, 8-amino,8-thiol, 8-thioalkyl, 8-hydroxyl and other 8-substituted adenines andguanines, 5-halo particularly 5-bromo, 5-trifluoromethyl and other5-substituted uracils and cytosines, 7-methylquanine and7-methyladenine, 8-azaguanine and 8-azaadenine, 7-deazaguanine and7-deazaadenine and 3-deazaguanine and 3-deazaadenine.

Further, nucleobases comprise those disclosed in U.S. Pat. No.3,687,808, those disclosed in “The Concise Encyclopedia of PolymerScience And Engineering”, pages 858-859, Kroschwitz, ed. John Wiley &Sons, 1990, those disclosed by Englisch et al., Angewandle Chemie,International Edition, 1991, 30, page 613, and those disclosed bySanghvi, Chapter 15, Antisense Research and Applications,” pages289-302, Crooke, and Lebleu, eds., CRC Press, 1993. Certain of thesenucleobases are particularly useful for increasing the binding affinityof the oligomeric compounds of the invention. These include5-substituted pyrimidines, 6-azapyrimidines and N-2, N-6 and 0-6substituted purines, comprising 2-aminopropyladenine, 5-propynyluraciland 5-propynylcytosine. 5-methylcytosine substitutions have been shownto increase nucleic acid duplex stability by 0.6-1.2<0>C (Sanghvi, etal., eds, “Antisense Research and Applications,” CRC Press, Boca Raton,1993, pp. 276-278) and are presently preferred base substitutions, evenmore particularly when combined with 2′-O-methoxyethyl sugarmodifications. Modified nucleobases are described in U.S. Pat. No.3,687,808, as well as U.S. Pat. Nos. 4,845,205; 5,130,302; 5,134,066;5,175,273; 5,367,066; 5,432,272; 5,457,187; 5,459,255; 5,484,908;5,502,177; 5,525,711; 5,552,540; 5,587,469; 5,596,091; 5,614,617;5,750,692, and 5,681,941, each of which is herein incorporated byreference.

In some embodiments, the single stranded oligonucleotides are chemicallylinked to one or more moieties or conjugates that enhance the activity,cellular distribution, or cellular uptake of the oligonucleotide. Forexample, one or more single stranded oligonucleotides, of the same ordifferent types, can be conjugated to each other; or single strandedoligonucleotides can be conjugated to targeting moieties with enhancedspecificity for a cell type or tissue type. Such moieties include, butare not limited to, lipid moieties such as a cholesterol moiety(Letsinger et al., Proc. Natl. Acad. Sci. USA, 1989, 86, 6553-6556),cholic acid (Manoharan et al., Bioorg. Med. Chem. Let., 1994, 4,1053-1060), a thioether, e.g., hexyl-S-tritylthiol (Manoharan et al,Ann. N.Y. Acad. Sci., 1992, 660, 306-309; Manoharan et al., Bioorg. Med.Chem. Let., 1993, 3, 2765-2770), a thiocholesterol (Oberhauser et al.,Nucl. Acids Res., 1992, 20, 533-538), an aliphatic chain, e.g.,dodecandiol or undecyl residues (Kabanov et al., FEBS Lett., 1990, 259,327-330; Svinarchuk et al., Biochimie, 1993, 75, 49-54), a phospholipid,e.g., di-hexadecyl-rac-glycerol or triethylammonium1,2-di-O-hexadecyl-rac-glycero-3-H-phosphonate (Manoharan et al.,Tetrahedron Lett., 1995, 36, 3651-3654; Shea et al., Nucl. Acids Res.,1990, 18, 3777-3783), a polyamine or a polyethylene glycol chain(Mancharan et al., Nucleosides & Nucleotides, 1995, 14, 969-973), oradamantane acetic acid (Manoharan et al., Tetrahedron Lett., 1995, 36,3651-3654), a palmityl moiety (Mishra et al., Biochim. Biophys. Acta,1995, 1264, 229-237), or an octadecylamine or hexylamino-carbonyl-toxycholesterol moiety (Crooke et al., J. Pharmacol. Exp. Ther., 1996,277, 923-937). See also U.S. Pat. Nos. 4,828,979; 4,948,882; 5,218,105;5,525,465; 5,541,313; 5,545,730; 5,552,538; 5,578,717, 5,580,731;5,580,731; 5,591,584; 5,109,124; 5,118,802; 5,138,045; 5,414,077;5,486,603; 5,512,439; 5,578,718; 5,608,046; 4,587,044; 4,605,735;4,667,025; 4,762,779; 4,789,737; 4,824,941; 4,835,263; 4,876,335;4,904,582; 4,958,013; 5,082,830; 5,112,963; 5,214,136; 5,082,830;5,112,963; 5,214,136; 5,245,022; 5,254,469; 5,258,506; 5,262,536;5,272,250; 5,292,873; 5,317,098; 5,371,241, 5,391,723; 5,416,203,5,451,463; 5,510,475; 5,512,667; 5,514,785; 5,565,552; 5,567,810;5,574,142; 5,585,481; 5,587,371; 5,595,726; 5,597,696; 5,599,923;5,599,928 and 5,688,941, each of which is herein incorporated byreference.

These moieties or conjugates can include conjugate groups covalentlybound to functional groups such as primary or secondary hydroxyl groups.Conjugate groups of the invention include intercalators, reportermolecules, polyamines, polyamides, polyethylene glycols, polyethers,groups that enhance the pharmacodynamic properties of oligomers, andgroups that enhance the pharmacokinetic properties of oligomers. Typicalconjugate groups include cholesterols, lipids, phospholipids, biotin,phenazine, folate, phenanthridine, anthraquinone, acridine,fluoresceins, rhodamines, coumarins, and dyes. Groups that enhance thepharmacodynamic properties, in the context of this invention, includegroups that improve uptake, enhance resistance to degradation, and/orstrengthen sequence-specific hybridization with the target nucleic acid.Groups that enhance the pharmacokinetic properties, in the context ofthis invention, include groups that improve uptake, distribution,metabolism or excretion of the compounds of the present invention.Representative conjugate groups are disclosed in International PatentApplication No. PCT/US92/09196, filed Oct. 23, 1992, and U.S. Pat. No.6,287,860, which are incorporated herein by reference. Conjugatemoieties include, but are not limited to, lipid moieties such as acholesterol moiety, cholic acid, a thioether, e.g., hexyl-5-tritylthiol,a thiocholesterol, an aliphatic chain, e.g., dodecandiol or undecylresidues, a phospholipid, e.g., di-hexadecyl-rac-glycerol ortriethylammonium 1,2-di-O-hexadecyl-rac-glycero-3-H-phosphonate, apolyamine or a polyethylene glycol chain, or adamantane acetic acid, apalmityl moiety, or an octadecylamine or hexylamino-carbonyl-oxycholesterol moiety. See, e.g., U.S. Pat. Nos. 4,828,979; 4,948,882;5,218,105; 5,525,465; 5,541,313; 5,545,730; 5,552,538; 5,578,717,5,580,731; 5,580,731; 5,591,584; 5,109,124; 5,118,802; 5,138,045;5,414,077; 5,486,603; 5,512,439; 5,578,718; 5,608,046; 4,587,044;4,605,735; 4,667,025; 4,762,779; 4,789,737; 4,824,941; 4,835,263;4,876,335; 4,904,582; 4,958,013; 5,082,830; 5,112,963; 5,214,136;5,082,830; 5,112,963; 5,214,136; 5,245,022; 5,254,469; 5,258,506;5,262,536; 5,272,250; 5,292,873; 5,317,098; 5,371,241, 5,391,723;5,416,203, 5,451,463; 5,510,475; 5,512,667; 5,514,785; 5,565,552;5,567,810; 5,574,142; 5,585,481; 5,587,371; 5,595,726; 5,597,696;5,599,923; 5,599,928 and 5,688,941.

In some embodiments, single stranded oligonucleotide modificationinclude modification of the 5′ or 3′ end of the oligonucleotide. In someembodiments, the 3′ end of the oligonucleotide comprises a hydroxylgroup or a thiophosphate. It should be appreciated that additionalmolecules (e.g. a biotin moiety or a fluorophor) can be conjugated tothe 5′ or 3′ end of the single stranded oligonucleotide. In someembodiments, the single stranded oligonucleotide comprises a biotinmoiety conjugated to the 5′ nucleotide.

In some embodiments, the single stranded oligonucleotide compriseslocked nucleic acids (LNA), ENA modified nucleotides, 2′-O-methylnucleotides, or 2′-fluoro-deoxyribonucleotides. In some embodiments, thesingle stranded oligonucleotide comprises alternatingdeoxyribonucleotides and 2′-fluoro-deoxyribonucleotides. In someembodiments, the single stranded oligonucleotide comprises alternatingdeoxyribonucleotides and 2′-O-methyl nucleotides. In some embodiments,the single stranded oligonucleotide comprises alternatingdeoxyribonucleotides and ENA modified nucleotides. In some embodiments,the single stranded oligonucleotide comprises alternatingdeoxyribonucleotides and locked nucleic acid nucleotides. In someembodiments, the single stranded oligonucleotide comprises alternatinglocked nucleic acid nucleotides and 2′-O-methyl nucleotides.

In some embodiments, the 5′ nucleotide of the oligonucleotide is adeoxyribonucleotide. In some embodiments, the 5′ nucleotide of theoligonucleotide is a locked nucleic acid nucleotide. In someembodiments, the nucleotides of the oligonucleotide comprisedeoxyribonucleotides flanked by at least one locked nucleic acidnucleotide on each of the 5′ and 3′ ends of the deoxyribonucleotides. Insome embodiments, the nucleotide at the 3′ position of theoligonucleotide has a 3′ hydroxyl group or a 3′ thiophosphate.

In some embodiments, the single stranded oligonucleotide comprisesphosphorothioate internucleotide linkages. In some embodiments, thesingle stranded oligonucleotide comprises phosphorothioateinternucleotide linkages between at least two nucleotides. In someembodiments, the single stranded oligonucleotide comprisesphosphorothioate internucleotide linkages between all nucleotides.

It should be appreciated that the single stranded oligonucleotide canhave any combination of modifications as described herein.

The oligonucleotide may comprise a nucleotide sequence having one ormore of the following modification patterns.

(a) (X)Xxxxxx, (X)xXxxxx, (X)xxXxxx, (X)xxxXxx, (X)xxxxXx and (X)xxxxxX,

(b) (X)XXxxxx, (X)XxXxxx, (X)XxxXxx, (X)XxxxXx, (X)XxxxxX, (X)xXXxxx,(x)xXxXxx, (X)xXxxXx, (X)xXxxxX, (X)xxXXxx, (X)xxXxXx, (X)xxXxxX,(X)xxxXXx, (X)xxxXxX and (X)xxxxXX,

(c) (X)XXXxxx, (X)xXXXxx, (X)xxXXXx, (X)xxxXXX, (X)XXxXxx, (X)XXxxXx,(x)XXxxxX, (X)xXXxXx, (X)xXXxxX, (X)xxXXxX, (X)XxXXxx, (X)XxxXXx(x)XxxxXX, (X)xXxXXx, (X)xXxxXX, (X)xxXxXX, (X)xXxXxX and (X)XxXxXx,

(d) (X)xxXXX, (X)xXxXXX, (X)xXXxXX, (X)xXXXxX, (X)xXXXXx, (X)XxxXXXX,(X)XxXxXX, (X)XxXXxX, (X)XxXXx, (X)XXxxXX, (X)XXxXxX, (x)XXxXXx,(X)XXXxxX, (X)XXXxXx, and (X)XXXXxx,

(e) (X)xXXXXX, (X)XxXXXX, (X)XXxXXX, (X)XXXxXX, (X)XXXXxX and (x)XXXXXx,and

(f) XXXXXX, XxXXXXX, XXxXXXX, XXXxXXX, XXXXxXX, XXXXXxX and XXXXXXx, inwhich “X” denotes a nucleotide analogue, (X) denotes an optionalnucleotide analogue, and “x” denotes a DNA or RNA nucleotide unit. Eachof the above listed patterns may appear one or more times within anoligonucleotide, alone or in combination with any of the other disclosedmodification patterns.

Methods for Modulating Gene Expression

In one aspect, the invention relates to methods for modulating geneexpression in a cell (e.g., a cell for which UTRN levels are reduced(e.g., a muscle cell)) for research purposes (e.g., to study thefunction of the gene in the cell). In another aspect, the inventionrelates to methods for modulating gene expression in a cell (e.g., acell for which UTRN levels are reduced) for gene or epigenetic therapy.The cells can be in vitro, ex vivo, or in vivo (e.g., in a subject whohas a disease resulting from reduced expression of UTRN, (e.g., amuscular dystrophy, including DMD, BMD, and myotonic dystrophy)). Insome embodiments, methods for modulating gene expression in a cellcomprise delivering a single stranded oligonucleotide as describedherein. In some embodiments, delivery of the single strandedoligonucleotide to the cell results in a level of expression of genethat is at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%,200% or more greater than a level of expression of gene in a controlcell to which the single stranded oligonucleotide has not beendelivered. In certain embodiments, delivery of the single strandedoligonucleotide to the cell results in a level of expression of genethat is at least 50% greater than a level of expression of gene in acontrol cell to which the single stranded oligonucleotide has not beendelivered.

In another aspect of the invention, methods comprise administering to asubject (e.g. a human) a composition comprising a single strandedoligonucleotide as described herein to increase protein levels in thesubject. In some embodiments, the increase in protein levels is at least5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, or more,higher than the amount of a protein in the subject before administering.

As another example, to increase expression of UTRN in a cell, themethods include introducing into the cell a single strandedoligonucleotide that is sufficiently complementary to a PRC2-associatedregion (e.g., of a long non-coding RNA) that maps to a genomic positionencompassing or in proximity to the UTRN gene.

In another aspect of the invention provides methods of treating acondition (e.g., MD) associated with decreased levels of expression ofUTRN in a subject, the method comprising administering a single strandedoligonucleotide as described herein.

A subject can include a non-human mammal, e.g. mouse, rat, guinea pig,rabbit, cat, dog, goat, cow, or horse. In preferred embodiments, asubject is a human. Single stranded oligonucleotides have been employedas therapeutic moieties in the treatment of disease states in animals,including humans. Single stranded oligonucleotides can be usefultherapeutic modalities that can be configured to be useful in treatmentregimes for the treatment of cells, tissues and animals, especiallyhumans.

For therapeutics, an animal, preferably a human, suspected of having MDis treated by administering single stranded oligonucleotide inaccordance with this invention. For example, in one non-limitingembodiment, the methods comprise the step of administering to the animalin need of treatment, a therapeutically effective amount of a singlestranded oligonucleotide as described herein.

Formulation, Delivery, And Dosing

The oligonucleotides described herein can be formulated foradministration to a subject for treating muscular dystrophies, includingDMD, BMD, and myotonic dystrophy. It should be understood that theformulations, compositions and methods can be practiced with any of theoligonucleotides disclosed herein.

The formulations may conveniently be presented in unit dosage form andmay be prepared by any methods well known in the art of pharmacy. Theamount of active ingredient (e.g., an oligonucleotide or compound of theinvention) which can be combined with a carrier material to produce asingle dosage form will vary depending upon the host being treated, theparticular mode of administration, e.g., intradermal or inhalation. Theamount of active ingredient which can be combined with a carriermaterial to produce a single dosage form will generally be that amountof the compound which produces a therapeutic effect, e.g. tumorregression.

Pharmaceutical formulations of this invention can be prepared accordingto any method known to the art for the manufacture of pharmaceuticals.Such formulations can contain sweetening agents, flavoring agents,coloring agents and preserving agents. A formulation can be admixturedwith nontoxic pharmaceutically acceptable excipients which are suitablefor manufacture. Formulations may comprise one or more diluents,emulsifiers, preservatives, buffers, excipients, etc. and may beprovided in such forms as liquids, powders, emulsions, lyophilizedpowders, sprays, creams, lotions, controlled release formulations,tablets, pills, gels, on patches, in implants, etc.

A formulated single stranded oligonucleotide composition can assume avariety of states. In some examples, the composition is at leastpartially crystalline, uniformly crystalline, and/or anhydrous (e.g.,less than 80, 50, 30, 20, or 10% water). In another example, the singlestranded oligonucleotide is in an aqueous phase, e.g., in a solutionthat includes water. The aqueous phase or the crystalline compositionscan, e.g., be incorporated into a delivery vehicle, e.g., a liposome(particularly for the aqueous phase) or a particle (e.g., amicroparticle as can be appropriate for a crystalline composition).Generally, the single stranded oligonucleotide composition is formulatedin a manner that is compatible with the intended method ofadministration.

In some embodiments, the composition is prepared by at least one of thefollowing methods: spray drying, lyophilization, vacuum drying,evaporation, fluid bed drying, or a combination of these techniques; orsonication with a lipid, freeze-drying, condensation and otherself-assembly.

A single stranded oligonucleotide preparation can be formulated oradministered (together or separately) in combination with another agent,e.g., another therapeutic agent or an agent that stabilizes a singlestranded oligonucleotide, e.g., a protein that complexes with singlestranded oligonucleotide. Still other agents include chelators, e.g.,EDTA (e.g., to remove divalent cations such as Mg²⁺), salts, RNAseinhibitors (e.g., a broad specificity RNAse inhibitor such as RNAsin)and so forth.

In one embodiment, the single stranded oligonucleotide preparationincludes another single stranded oligonucleotide, e.g., a second singlestranded oligonucleotide that modulates expression of a second gene or asecond single stranded oligonucleotide that modulates expression of thefirst gene. Still other preparation can include at least 3, 5, ten,twenty, fifty, or a hundred or more different single strandedoligonucleotide species. Such single stranded oligonucleotides canmediated gene expression with respect to a similar number of differentgenes. In one embodiment, the single stranded oligonucleotidepreparation includes at least a second therapeutic agent (e.g., an agentother than an oligonucleotide).

Route of Delivery

A composition that includes a single stranded oligonucleotide can bedelivered to a subject by a variety of routes. Exemplary routes include:intravenous, intradermal, topical, rectal, parenteral, anal,intravaginal, intranasal, pulmonary, ocular. The term “therapeuticallyeffective amount” is the amount of oligonucleotide present in thecomposition that is needed to provide the desired level of UTRNexpression in the subject to be treated to give the anticipatedphysiological response. The term “physiologically effective amount” isthat amount delivered to a subject to give the desired palliative orcurative effect. The term “pharmaceutically acceptable carrier” meansthat the carrier can be administered to a subject with no significantadverse toxicological effects to the subject.

The single stranded oligonucleotide molecules of the invention can beincorporated into pharmaceutical compositions suitable foradministration. Such compositions typically include one or more speciesof single stranded oligonucleotide and a pharmaceutically acceptablecarrier. As used herein the language “pharmaceutically acceptablecarrier” is intended to include any and all solvents, dispersion media,coatings, antibacterial and antifungal agents, isotonic and absorptiondelaying agents, and the like, compatible with pharmaceuticaladministration. The use of such media and agents for pharmaceuticallyactive substances is well known in the art. Except insofar as anyconventional media or agent is incompatible with the active compound,use thereof in the compositions is contemplated. Supplementary activecompounds can also be incorporated into the compositions.

The pharmaceutical compositions of the present invention may beadministered in a number of ways depending upon whether local orsystemic treatment is desired and upon the area to be treated.Administration may be topical (including ophthalmic, vaginal, rectal,intranasal, transdermal), oral or parenteral. Parenteral administrationincludes intravenous drip, subcutaneous, intraperitoneal orintramuscular injection, or intrathecal or intraventricularadministration.

The route and site of administration may be chosen to enhance targeting.For example, to target muscle cells, intramuscular injection into themuscles of interest would be a logical choice. Lung cells might betargeted by administering the single stranded oligonucleotide in aerosolform. The vascular endothelial cells could be targeted by coating aballoon catheter with the single stranded oligonucleotide andmechanically introducing the oligonucleotide.

Topical administration refers to the delivery to a subject by contactingthe formulation directly to a surface of the subject. The most commonform of topical delivery is to the skin, but a composition disclosedherein can also be directly applied to other surfaces of the body, e.g.,to the eye, a mucous membrane, to surfaces of a body cavity or to aninternal surface. As mentioned above, the most common topical deliveryis to the skin. The term encompasses several routes of administrationincluding, but not limited to, topical and transdermal. These modes ofadministration typically include penetration of the skin's permeabilitybarrier and efficient delivery to the target tissue or stratum. Topicaladministration can be used as a means to penetrate the epidermis anddermis and ultimately achieve systemic delivery of the composition.Topical administration can also be used as a means to selectivelydeliver oligonucleotides to the epidermis or dermis of a subject, or tospecific strata thereof, or to an underlying tissue.

Formulations for topical administration may include transdermal patches,ointments, lotions, creams, gels, drops, suppositories, sprays, liquidsand powders. Conventional pharmaceutical carriers, aqueous, powder oroily bases, thickeners and the like may be necessary or desirable.Coated condoms, gloves and the like may also be useful.

Transdermal delivery is a valuable route for the administration of lipidsoluble therapeutics. The dermis is more permeable than the epidermisand therefore absorption is much more rapid through abraded, burned ordenuded skin. Inflammation and other physiologic conditions thatincrease blood flow to the skin also enhance transdermal adsorption.Absorption via this route may be enhanced by the use of an oily vehicle(inunction) or through the use of one or more penetration enhancers.Other effective ways to deliver a composition disclosed herein via thetransdermal route include hydration of the skin and the use ofcontrolled release topical patches. The transdermal route provides apotentially effective means to deliver a composition disclosed hereinfor systemic and/or local therapy. In addition, iontophoresis (transferof ionic solutes through biological membranes under the influence of anelectric field), phonophoresis or sonophoresis (use of ultrasound toenhance the absorption of various therapeutic agents across biologicalmembranes, notably the skin and the cornea), and optimization of vehiclecharacteristics relative to dose position and retention at the site ofadministration may be useful methods for enhancing the transport oftopically applied compositions across skin and mucosal sites.

Both the oral and nasal membranes offer advantages over other routes ofadministration. For example, oligonucleotides administered through thesemembranes may have a rapid onset of action, provide therapeutic plasmalevels, avoid first pass effect of hepatic metabolism, and avoidexposure of the oligonucleotides to the hostile gastrointestinal (GI)environment. Additional advantages include easy access to the membranesites so that the oligonucleotide can be applied, localized and removedeasily.

In oral delivery, compositions can be targeted to a surface of the oralcavity, e.g., to sublingual mucosa which includes the membrane ofventral surface of the tongue and the floor of the mouth or the buccalmucosa which constitutes the lining of the cheek. The sublingual mucosais relatively permeable thus giving rapid absorption and acceptablebioavailability of many agents. Further, the sublingual mucosa isconvenient, acceptable and easily accessible.

A pharmaceutical composition of single stranded oligonucleotide may alsobe administered to the buccal cavity of a human being by spraying intothe cavity, without inhalation, from a metered dose spray dispenser, amixed micellar pharmaceutical formulation as described above and apropellant. In one embodiment, the dispenser is first shaken prior tospraying the pharmaceutical formulation and propellant into the buccalcavity.

Compositions for oral administration include powders or granules,suspensions or solutions in water, syrups, slurries, emulsions, elixirsor non-aqueous media, tablets, capsules, lozenges, or troches. In thecase of tablets, carriers that can be used include lactose, sodiumcitrate and salts of phosphoric acid. Various disintegrants such asstarch, and lubricating agents such as magnesium stearate, sodium laurylsulfate and talc, are commonly used in tablets. For oral administrationin capsule form, useful diluents are lactose and high molecular weightpolyethylene glycols. When aqueous suspensions are required for oraluse, the nucleic acid compositions can be combined with emulsifying andsuspending agents. If desired, certain sweetening and/or flavoringagents can be added.

Parenteral administration includes intravenous drip, subcutaneous,intraperitoneal or intramuscular injection, intrathecal orintraventricular administration. In some embodiments, parentaladministration involves administration directly to the site of disease(e.g. injection into a tumor).

Formulations for parenteral administration may include sterile aqueoussolutions which may also contain buffers, diluents and other suitableadditives. Intraventricular injection may be facilitated by anintraventricular catheter, for example, attached to a reservoir. Forintravenous use, the total concentration of solutes should be controlledto render the preparation isotonic.

Any of the single stranded oligonucleotides described herein can beadministered to ocular tissue. For example, the compositions can beapplied to the surface of the eye or nearby tissue, e.g., the inside ofthe eyelid. For ocular administration, ointments or droppable liquidsmay be delivered by ocular delivery systems known to the art such asapplicators or eye droppers. Such compositions can include mucomimeticssuch as hyaluronic acid, chondroitin sulfate, hydroxypropylmethylcellulose or poly(vinyl alcohol), preservatives such as sorbicacid, EDTA or benzylchronium chloride, and the usual quantities ofdiluents and/or carriers. The single stranded oligonucleotide can alsobe administered to the interior of the eye, and can be introduced by aneedle or other delivery device which can introduce it to a selectedarea or structure.

Pulmonary delivery compositions can be delivered by inhalation by thepatient of a dispersion so that the composition, preferably singlestranded oligonucleotides, within the dispersion can reach the lungwhere it can be readily absorbed through the alveolar region directlyinto blood circulation. Pulmonary delivery can be effective both forsystemic delivery and for localized delivery to treat diseases of thelungs.

Pulmonary delivery can be achieved by different approaches, includingthe use of nebulized, aerosolized, micellular and dry powder-basedformulations. Delivery can be achieved with liquid nebulizers,aerosol-based inhalers, and dry powder dispersion devices. Metered-dosedevices are preferred. One of the benefits of using an atomizer orinhaler is that the potential for contamination is minimized because thedevices are self-contained. Dry powder dispersion devices, for example,deliver agents that may be readily formulated as dry powders. A singlestranded oligonucleotide composition may be stably stored as lyophilizedor spray-dried powders by itself or in combination with suitable powdercarriers. The delivery of a composition for inhalation can be mediatedby a dosing timing element which can include a timer, a dose counter,time measuring device, or a time indicator which when incorporated intothe device enables dose tracking, compliance monitoring, and/or dosetriggering to a patient during administration of the aerosol medicament.

The term “powder” means a composition that consists of finely dispersedsolid particles that are free flowing and capable of being readilydispersed in an inhalation device and subsequently inhaled by a subjectso that the particles reach the lungs to permit penetration into thealveoli. Thus, the powder is said to be “respirable.” Preferably theaverage particle size is less than about 10 μm in diameter preferablywith a relatively uniform spheroidal shape distribution. More preferablythe diameter is less than about 7.5 μm and most preferably less thanabout 5.0 μm. Usually the particle size distribution is between about0.1 μm and about 5 μm in diameter, particularly about 0.3 μm to about 5μm.

The term “dry” means that the composition has a moisture content belowabout 10% by weight (% w) water, usually below about 5% w and preferablyless it than about 3% w. A dry composition can be such that theparticles are readily dispersible in an inhalation device to form anaerosol.

The types of pharmaceutical excipients that are useful as carrierinclude stabilizers such as human serum albumin (HSA), bulking agentssuch as carbohydrates, amino acids and polypeptides; pH adjusters orbuffers; salts such as sodium chloride; and the like. These carriers maybe in a crystalline or amorphous form or may be a mixture of the two.

Suitable pH adjusters or buffers include organic salts prepared fromorganic acids and bases, such as sodium citrate, sodium ascorbate, andthe like; sodium citrate is preferred. Pulmonary administration of amicellar single stranded oligonucleotide formulation may be achievedthrough metered dose spray devices with propellants such astetrafluoroethane, heptafluoroethane, dimethylfluoropropane,tetrafluoropropane, butane, isobutane, dimethyl ether and other non-CFCand CFC propellants.

Exemplary devices include devices which are introduced into thevasculature, e.g., devices inserted into the lumen of a vascular tissue,or which devices themselves form a part of the vasculature, includingstents, catheters, heart valves, and other vascular devices. Thesedevices, e.g., catheters or stents, can be placed in the vasculature ofthe lung, heart, or leg.

Other devices include non-vascular devices, e.g., devices implanted inthe peritoneum, or in organ or glandular tissue, e.g., artificialorgans. The device can release a therapeutic substance in addition to asingle stranded oligonucleotide, e.g., a device can release insulin.

In one embodiment, unit doses or measured doses of a composition thatincludes single stranded oligonucleotide are dispensed by an implanteddevice. The device can include a sensor that monitors a parameter withina subject. For example, the device can include pump, e.g., and,optionally, associated electronics.

Tissue, e.g., cells or organs can be treated with a single strandedoligonucleotide, ex vivo and then administered or implanted in asubject. The tissue can be autologous, allogeneic, or xenogeneic tissue.E.g., tissue can be treated to reduce graft v. host disease. In otherembodiments, the tissue is allogeneic and the tissue is treated to treata disorder characterized by unwanted gene expression in that tissue.E.g., tissue, e.g., hematopoietic cells, e.g., bone marrow hematopoieticcells, can be treated to inhibit unwanted cell proliferation.Introduction of treated tissue, whether autologous or transplant, can becombined with other therapies. In some implementations, the singlestranded oligonucleotide treated cells are insulated from other cells,e.g., by a semi-permeable porous barrier that prevents the cells fromleaving the implant, but enables molecules from the body to reach thecells and molecules produced by the cells to enter the body. In oneembodiment, the porous barrier is formed from alginate.

In one embodiment, a contraceptive device is coated with or contains asingle stranded oligonucleotide. Exemplary devices include condoms,diaphragms, IUD (implantable uterine devices, sponges, vaginal sheaths,and birth control devices.

Dosage

In one aspect, the invention features a method of administering a singlestranded oligonucleotide (e.g., as a compound or as a component of acomposition) to a subject (e.g., a human subject). In one embodiment,the unit dose is between about 10 mg and 25 mg per kg of bodyweight. Inone embodiment, the unit dose is between about 1 mg and 100 mg per kg ofbodyweight. In one embodiment, the unit dose is between about 0.1 mg and500 mg per kg of bodyweight. In some embodiments, the unit dose is morethan 0.001, 0.005, 0.01, 0.05, 0.1, 0.5, 1, 2, 5, 10, 25, 50 or 100 mgper kg of bodyweight.

The defined amount can be an amount effective to treat or prevent adisease or disorder, e.g., a disease or disorder associated with theUTRN. The unit dose, for example, can be administered by injection(e.g., intravenous or intramuscular), an inhaled dose, or a topicalapplication.

In some embodiments, the unit dose is administered daily. In someembodiments, less frequently than once a day, e.g., less than every 2,4, 8 or 30 days. In another embodiment, the unit dose is notadministered with a frequency (e.g., not a regular frequency). Forexample, the unit dose may be administered a single time. In someembodiments, the unit dose is administered more than once a day, e.g.,once an hour, two hours, four hours, eight hours, twelve hours, etc.

In one embodiment, a subject is administered an initial dose and one ormore maintenance doses of a single stranded oligonucleotide. Themaintenance dose or doses are generally lower than the initial dose,e.g., one-half less of the initial dose. A maintenance regimen caninclude treating the subject with a dose or doses ranging from 0.0001 to100 mg/kg of body weight per day, e.g., 100, 10, 1, 0.1, 0.01, 0.001, or0.0001 mg per kg of bodyweight per day. The maintenance doses may beadministered no more than once every 1, 5, 10, or 30 days. Further, thetreatment regimen may last for a period of time which will varydepending upon the nature of the particular disease, its severity andthe overall condition of the patient. In some embodiments the dosage maybe delivered no more than once per day, e.g., no more than once per 24,36, 48, or more hours, e.g., no more than once for every 5 or 8 days.Following treatment, the patient can be monitored for changes in hiscondition and for alleviation of the symptoms of the disease state. Thedosage of the oligonucleotide may either be increased in the event thepatient does not respond significantly to current dosage levels, or thedose may be decreased if an alleviation of the symptoms of the diseasestate is observed, if the disease state has been ablated, or ifundesired side-effects are observed.

The effective dose can be administered in a single dose or in two ormore doses, as desired or considered appropriate under the specificcircumstances. If desired to facilitate repeated or frequent infusions,implantation of a delivery device, e.g., a pump, semi-permanent stent(e.g., intravenous, intraperitoneal, intracisternal or intracapsular),or reservoir may be advisable.

In some embodiments, the oligonucleotide pharmaceutical compositionincludes a plurality of single stranded oligonucleotide species. Inanother embodiment, the single stranded oligonucleotide species hassequences that are non-overlapping and non-adjacent to another specieswith respect to a naturally occurring target sequence (e.g., aPRC2-associated region). In another embodiment, the plurality of singlestranded oligonucleotide species is specific for differentPRC2-associated regions. In another embodiment, the single strandedoligonucleotide is allele specific. In some cases, a patient is treatedwith a single stranded oligonucleotide in conjunction with othertherapeutic modalities.

Following successful treatment, it may be desirable to have the patientundergo maintenance therapy to prevent the recurrence of the diseasestate, wherein the compound of the invention is administered inmaintenance doses, ranging from 0.0001 mg to 100 mg per kg of bodyweight.

The concentration of the single stranded oligonucleotide composition isan amount sufficient to be effective in treating or preventing adisorder or to regulate a physiological condition in humans. Theconcentration or amount of single stranded oligonucleotide administeredwill depend on the parameters determined for the agent and the method ofadministration, e.g. nasal, buccal, pulmonary. For example, nasalformulations may tend to require much lower concentrations of someingredients in order to avoid irritation or burning of the nasalpassages. It is sometimes desirable to dilute an oral formulation up to10-100 times in order to provide a suitable nasal formulation.

Certain factors may influence the dosage required to effectively treat asubject, including but not limited to the severity of the disease ordisorder, previous treatments, the general health and/or age of thesubject, and other diseases present. Moreover, treatment of a subjectwith a therapeutically effective amount of a single strandedoligonucleotide can include a single treatment or, preferably, caninclude a series of treatments. It will also be appreciated that theeffective dosage of a single stranded oligonucleotide used for treatmentmay increase or decrease over the course of a particular treatment. Forexample, the subject can be monitored after administering a singlestranded oligonucleotide composition. Based on information from themonitoring, an additional amount of the single stranded oligonucleotidecomposition can be administered.

Dosing is dependent on severity and responsiveness of the diseasecondition to be treated, with the course of treatment lasting fromseveral days to several months, or until a cure is effected or adiminution of disease state is achieved. Optimal dosing schedules can becalculated from measurements of UTRN expression levels in the body ofthe patient. Persons of ordinary skill can easily determine optimumdosages, dosing methodologies and repetition rates. Optimum dosages mayvary depending on the relative potency of individual compounds, and cangenerally be estimated based on EC50s found to be effective in in vitroand in vivo animal models. In some embodiments, the animal modelsinclude transgenic animals that express a human UTRN. In anotherembodiment, the composition for testing includes a single strandedoligonucleotide that is complementary, at least in an internal region,to a sequence that is conserved between UTRN in the animal model and theUTRN in a human.

In one embodiment, the administration of the single strandedoligonucleotide composition is parenteral, e.g. intravenous (e.g., as abolus or as a diffusible infusion), intradermal, intraperitoneal,intramuscular, intrathecal, intraventricular, intracranial,subcutaneous, transmucosal, buccal, sublingual, endoscopic, rectal,oral, vaginal, topical, pulmonary, intranasal, urethral or ocular.Administration can be provided by the subject or by another person,e.g., a health care provider. The composition can be provided inmeasured doses or in a dispenser which delivers a metered dose. Selectedmodes of delivery are discussed in more detail below.

Kits

In certain aspects of the invention, kits are provided, comprising acontainer housing a composition comprising a single strandedoligonucleotide. In some embodiments, the composition is apharmaceutical composition comprising a single stranded oligonucleotideand a pharmaceutically acceptable carrier. In some embodiments, theindividual components of the pharmaceutical composition may be providedin one container. Alternatively, it may be desirable to provide thecomponents of the pharmaceutical composition separately in two or morecontainers, e.g., one container for single stranded oligonucleotides,and at least another for a carrier compound. The kit may be packaged ina number of different configurations such as one or more containers in asingle box. The different components can be combined, e.g., according toinstructions provided with the kit. The components can be combinedaccording to a method described herein, e.g., to prepare and administera pharmaceutical composition. The kit can also include a deliverydevice.

The present invention is further illustrated by the following Examples,which in no way should be construed as further limiting. The entirecontents of all of the references (including literature references,issued patents, published patent applications, and co-pending patentapplications) cited throughout this application are hereby expresslyincorporated by reference.

EXAMPLES

The invention is further described in the following examples, which donot limit the scope of the invention described in the claims.

Materials and Methods: Real Time PCR

RNA was harvested from the cells using Promega SV 96 Total RNA Isolationsystem or Trizol omitting the DNAse step. In separate pilot experiments,50 ng of RNA was determined to be sufficient template for the reversetranscriptase reaction. RNA harvested from cells was normalized so that50 ng of RNA was input to each reverse transcription reaction. For thefew samples that were too dilute to reach this limit, the maximum inputvolume was added. Reverse transcriptase reaction was performed using theSuperscript II kit and real time PCR performed on cDNA samples usingicycler SYBR green chemistry (Biorad). A baseline level of mRNAexpression for UTRN was determined through quantitative PCR as outlinedabove. Baseline levels were also determined for mRNA of varioushousekeeping genes which are constitutively expressed. A “control”housekeeping gene with approximately the same level of baselineexpression as the target gene was chosen for comparison purposes.

Cell Culture

Human hepatocyte Hep3B, human hepatocyte HepG2 cells, mouse hepatomaHepa1-6 cells, and human renal proximal tubule epithelial cells (RPTEC)were cultured using conditions known in the art (see, e.g. CurrentProtocols in Cell Biology). Details of the cell lines used in theexperiments described herein are provided in Table 5.

TABLE 5 Cell lines Culture Cell Line Source Species Gender Type TissueStatus Conditions RD RMS ATCC human F rhabdomyosarcoma skeletalimmortalized DMEM + muscle 10% FBS HSKM Gibco human M muscle skeletalnormal DMEM + muscle 10% FBS SK-N-AS ATCC human F neuroblast brainimmortalized MEM + 10% FBS am002fDMD DVBiologics human M muscle skeletalnormal M-gro + muscle supplement

Oligonucleotide Design

Oligonucleotides were designed within PRC2-interacting regions in orderto upregulate UTRN. The sequence and structure of each oligonucleotideis shown in Table 2.

The following table provides a description of the nucleotide analogs,modifications and intranucleotide linkages used for certainoligonucleotides tested and described in Table 2.

TABLE 3 Oligonucleotide Modifications Symbol Feature Description bio 5′biotin dAs DNA w/3′ thiophosphate dCs DNA w/3′ thiophosphate dGs DNAw/3′ thiophosphate dTs DNA w/3′ thiophosphate dG DNA w/3′ phosphate dUdeoxyuridine w/3′ phosphate enaAs ENA w/3′ thiophosphate enaCs ENA w/3′thiophosphate enaGs ENA w/3′ thiophosphate enaTs ENA w/3′ thiophosphatefluAs 2′-fluoro w/3′ thiophosphate fluCs 2′-fluoro w/3′ thiophosphatefluGs 2′-fluoro w/3′ thiophosphate fluUs 2′-fluoro w/3′ thiophosphateInaAs LNA w/3′ thiophosphate InaCs LNA w/3′ thiophosphate InaGs LNA w/3′thiophosphate InaTs LNA w/3′ thiophosphate omeAs 2′-OMe w/3′thiophosphate omeCs 2′-OMe w/3′ thiophosphate omeGs 2′-OMe w/3′thiophosphate omeTs 2′-OMe w/3′ thiophosphate InaAs-Sup LNA w/3′thiophosphate at 3′ terminus InaCs-Sup LNA w/3′ thiophosphate at 3′terminus InaGs-Sup LNA w/3′ thiophosphate at 3′ terminus InaTs-Sup LNAw/3′ thiophosphate at 3′ terminus InaA-Sup LNA w/3′ OH at 3′ terminusInaC-Sup LNA w/3′ OH at 3′ terminus InaG-Sup LNA w/3′ OH at 3′ terminusInaT-Sup LNA w/3′ OH at 3′ terminus omeA-Sup 2′-OMe w/3′ OH at 3′terminus omeC-Sup 2′-OMe w/3′ OH at 3′ terminus omeG-Sup 2′-OMe w/3′ OHat 3′ terminus omeU-Sup 2′-OMe w/3′ OH at 3′ terminus dAs-Sup DNA w/3′thiophosphate at 3′ terminus dCs-Sup DNA w/3′ thiophosphate at 3′terminus dGs-Sup DNA w/3′ thiophosphate at 3′ terminus dTs-Sup DNA w/3′thiophosphate at 3′ terminus dA-Sup DNA w/3′ OH at 3′ terminus dC-SupDNA w/3′ OH at 3′ terminus dG-Sup DNA w/3′ OH at 3′ terminusIn Vitro Transfection of Cells with Oligonucleotides

Cells were seeded into each well of 24-well plates at a density of25,000 cells per 500 uL and transfections were performed withLipofectamine and the single stranded oligonucleotides. Control wellscontained Lipofectamine alone. At 48 hours post-transfection,approximately 200 uL of cell culture supernatants were stored at −80 Cfor ELISA. At 48 hours post-transfection, RNA was harvested from thecells and quantitative PCR was carried out as outlined above. Thepercent induction of target mRNA expression by each oligonucleotide wasdetermined by normalizing mRNA levels in the presence of theoligonucleotide to the mRNA levels in the presence of control(Lipofectamine alone). This was compared side-by-side with the increasein mRNA expression of the “control” housekeeping gene.

Results: In Vitro Delivery of Single Stranded OligonucleotidesUpregulated UTRN Expression

Oligonucleotides were designed as candidates for upregulating UTRNexpression. A total of 65 single stranded oligonucleotides were designedto be complementary to a PRC2-interacting region within a sequence asset forth in SEQ ID NO: 1 or 2. Each of the oligonucleotides was testedin at least duplicate. The sequence and structural features of theoligonucleotides are set forth in Table 2. Briefly, cells weretransfected in vitro with each of the oligonucleotides as describedabove. UTRN expression in cells following treatment was evaluated byqRT-PCR. Oligonucleotides that upregulated UTRN expression wereidentified. Further details are outlined in Table 2.

Tables

TABLE 1 Hexamers that are not seed sequences of human miRNAsAAAAAA, AAAAAG, AAAACA, AAAAGA, AAAAGC, AAAAGG, AAAAUA, AAACAA, AAACAC, AAACAG,AAACAU, AAACCC, AAACCU, AAACGA, AAACGC, AAACGU, AAACUA, AAACUC, AAACUU, AAAGAU,AAAGCC, AAAGGA, AAAGGG, AAAGUC, AAAUAC, AAAUAU, AAAUCG, AAAUCU, AAAUGC, AAAUGU,AAAUUA, AAAUUG, AACAAC, AACAAG, AACAAU, AACACA, AACACG, AACAGA, AACAGC, AACAGG,AACAUC, AACAUG, AACCAA, AACCAC, AACCAG, AACCAU, AACCCC, AACCCG, AACCGA, AACCGC,AACCGG, AACCUA, AACCUU, AACGAA, AACGAC, AACGAG, AACGAU, AACGCU, AACGGG, AACGGU,AACGUA, AACGUC, AACGUG, AACGUU, AACUAU, AACUCA, AACUCC, AACUCG, AACUGA, AACUGC,AACUGU, AACUUA, AACUUC, AACUUG, AACUUU, AAGAAA, AAGAAG, AAGAAU, AAGACG, AAGAGA,AAGAGC, AAGAGG, AAGAGU, AAGAUU, AAGCAA, AAGCAC, AAGCAG, AAGCAU, AAGCCA, AAGCCC,AAGCCG, AAGCCU, AAGCGA, AAGCGG, AAGCGU, AAGCUA, AAGGAA, AAGGAC, AAGGCU, AAGGGC,AAGGGU, AAGGUU, AAGUAA, AAGUAC, AAGUAU, AAGUCC, AAGUCG, AAGUGA, AAGUGG, AAGUUA,AAGUUU, AAUAAA, AAUAAC, AAUAAG, AAUAAU, AAUACA, AAUACC, AAUACG, AAUAGA, AAUAGC,AAUAGG, AAUAGU, AAUAUC, AAUAUU, AAUCAA, AAUCAU, AAUCCA, AAUCCC, AAUCCG, AAUCGA,AAUCGC, AAUCGU, AAUCUA, AAUCUG, AAUCUU, AAUGAA, AAUGAC, AAUGAG, AAUGAU, AAUGCG,AAUGCU, AAUGGA, AAUGGU, AAUGUA, AAUGUC, AAUGUG, AAUUAA, AAUUAC, AAUUAG, AAUUCC,AAUUCG, AAUUGA, AAUUGG, AAUUGU, AAUUUC, AAUUUG, ACAAAA, ACAAAC, ACAAAG, ACAAAU,ACAACC, ACAACG, ACAACU, ACAAGA, ACAAGC, ACAAGU, ACAAUC, ACAAUG, ACAAUU, ACACAG,ACACCA, ACACCC, ACACCG, ACACCU, ACACGA, ACACGC, ACACGU, ACACUC, ACACUG, ACACUU,ACAGAA, ACAGAC, ACAGCC, ACAGCG, ACAGCU, ACAGGG, ACAGUC, ACAGUG, ACAGUU, ACAUAA,ACAUAC, ACAUCC, ACAUCG, ACAUCU, ACAUGA, ACAUGC, ACAUGU, ACAUUG, ACAUUU, ACCAAA,ACCAAC, ACCAAG, ACCAAU, ACCACC, ACCACG, ACCAGA, ACCAGU, ACCAUA, ACCAUG, ACCAUU,ACCCAA, ACCCAC, ACCCCA, ACCCCG, ACCCGA, ACCCGC, ACCCUA, ACCCUC, ACCCUU, ACCGAA,ACCGAC, ACCGAU, ACCGCA, ACCGCC, ACCGCG, ACCGCU, ACCGGA, ACCGGC, ACCGGU, ACCGUA,ACCGUC, ACCGUG, ACCGUU, ACCUAA, ACCUAC, ACCUAG, ACCUAU, ACCUCA, ACCUCC, ACCUCG,ACCUCU, ACCUGA, ACCUGC, ACCUGU, ACCUUA, ACCUUC, ACCUUU, ACGAAA, ACGAAC, ACGAAG,ACGAAU, ACGACA, ACGACC, ACGACG, ACGACU, ACGAGA, ACGAGC, ACGAGG, ACGAGU, ACGAUA,ACGAUC, ACGAUG, ACGAUU, ACGCAA, ACGCAG, ACGCAU, ACGCCC, ACGCCG, ACGCCU, ACGCGA,ACGCGG, ACGCGU, ACGCUA, ACGCUG, ACGCUU, ACGGAA, ACGGAC, ACGGAG, ACGGAU, ACGGCC,ACGGCG, ACGGCU, ACGGGC, ACGGGG, ACGGGU, ACGGUA, ACGGUC, ACGGUG, ACGGUU, ACGUAA,ACGUAC, ACGUAU, ACGUCC, ACGUCG, ACGUCU, ACGUGA, ACGUGC, ACGUGG, ACGUGU, ACGUUA,ACGUUC, ACGUUG, ACGUUU, ACUAAA, ACUAAG, ACUAAU, ACUACA, ACUACC, ACUACG, ACUACU,ACUAGG, ACUAUC, ACUAUG, ACUAUU, ACUCAU, ACUCCC, ACUCCG, ACUCCU, ACUCGA, ACUCGC,ACUCGG, ACUCUC, ACUCUU, ACUGAG, ACUGAU, ACUGCC, ACUGCG, ACUGCU, ACUGGG, ACUGGU,ACUGUC, ACUUAA, ACUUAC, ACUUAU, ACUUCA, ACUUCC, ACUUCG, ACUUCU, ACUUGA, ACUUGC,ACUUGU, ACUUUA, ACUUUC, ACUUUG, AGAAAA, AGAAAC, AGAAAG, AGAACC, AGAACG, AGAACU,AGAAGC, AGAAGU, AGAAUA, AGAAUC, AGAAUG, AGAAUU, AGACAA, AGACAC, AGACAU, AGACCA,AGACCC, AGACCG, AGACCU, AGACGA, AGACGC, AGACGU, AGACUA, AGACUC, AGACUU, AGAGAC,AGAGAG, AGAGAU, AGAGCC, AGAGCG, AGAGCU, AGAGGC, AGAGGG, AGAGGU, AGAGUA, AGAGUU,AGAUAC, AGAUAG, AGAUAU, AGAUCC, AGAUCG, AGAUCU, AGAUGA, AGAUGC, AGAUGG, AGAUUA,AGAUUC, AGAUUG, AGAUUU, AGCAAC, AGCACA, AGCACG, AGCACU, AGCAGA, AGCAUA, AGCAUC,AGCAUG, AGCCAA, AGCCAU, AGCCCA, AGCCGA, AGCCGC, AGCCGG, AGCCGU, AGCCUA, AGCCUC,AGCGAA, AGCGAG, AGCGAU, AGCGCA, AGCGCC, AGCGCG, AGCGCU, AGCGGA, AGCGGC, AGCGGU,AGCGUA, AGCGUC, AGCGUG, AGCGUU, AGCUAA, AGCUAC, AGCUAG, AGCUAU, AGCUCA, AGCUCC,AGCUCG, AGCUCU, AGCUGA, AGCUGG, AGCUGU, AGCUUC, AGCUUU, AGGAAU, AGGACC, AGGACG,AGGAGA, AGGAGU, AGGAUA, AGGCAA, AGGCAU, AGGCCG, AGGCGA, AGGCGC, AGGCGG, AGGCUA,AGGCUC, AGGCUU, AGGGAC, AGGGAU, AGGGGA, AGGGGU, AGGGUA, AGGGUG, AGGUAA,AGGUAC, AGGUCA, AGGUCC, AGGUCU, AGGUGA, AGGUGC, AGGUGG, AGGUGU, AGGUUC,AGGUUG, AGUAAA, AGUAAG, AGUAAU, AGUACA, AGUACG, AGUAGC, AGUAGG, AGUAUA, AGUAUC,AGUAUG, AGUAUU, AGUCAA, AGUCAC, AGUCAG, AGUCAU, AGUCCA, AGUCCG, AGUCCU, AGUCGA,AGUCGC, AGUCGG, AGUCGU, AGUCUA, AGUCUC, AGUCUG, AGUCUU, AGUGAA, AGUGAC, AGUGCG,AGUGGG, AGUGUC, AGUUAA, AGUUAC, AGUUAG, AGUUCC, AGUUCG, AGUUGA, AGUUGC,AGUUGU, AGUUUA, AGUUUC, AGUUUG, AGUUUU, AUAAAC, AUAAAU, AUAACA, AUAACC, AUAACG,AUAACU, AUAAGA, AUAAGC, AUAAGG, AUAAGU, AUAAUC, AUAAUG, AUAAUU, AUACAC, AUACAG,AUACAU, AUACCA, AUACCC, AUACCG, AUACGA, AUACGC, AUACGG, AUACGU, AUACUA, AUACUC,AUACUG, AUACUU, AUAGAA, AUAGAC, AUAGAU, AUAGCA, AUAGCG, AUAGCU, AUAGGA, AUAGGU,AUAGUA, AUAGUC, AUAGUG, AUAGUU, AUAUAC, AUAUAG, AUAUCC, AUAUCG, AUAUCU, AUAUGA,AUAUGC, AUAUGG, AUAUGU, AUAUUC, AUAUUG, AUAUUU, AUCAAA, AUCAAC, AUCAAG, AUCAAU,AUCACA, AUCACC, AUCACG, AUCAGC, AUCAGG, AUCCAA, AUCCAU, AUCCCC, AUCCCG, AUCCGA,AUCCGC, AUCCGG, AUCCUA, AUCCUC, AUCCUG, AUCGAA, AUCGAC, AUCGAG, AUCGAU, AUCGCA,AUCGCC, AUCGCG, AUCGCU, AUCGGC, AUCGGG, AUCGGU, AUCGUC, AUCGUG, AUCGUU, AUCUAA,AUCUAC, AUCUAG, AUCUAU, AUCUCC, AUCUCG, AUCUGU, AUCUUG, AUCUUU, AUGAAA, AUGAAC,AUGAAG, AUGAAU, AUGACC, AUGACU, AUGAGG, AUGAGU, AUGAUA, AUGAUC, AUGAUU, AUGCAA,AUGCAG, AUGCCA, AUGCCC, AUGCCG, AUGCGA, AUGCGG, AUGCGU, AUGCUC, AUGCUU, AUGGAC,AUGGCC, AUGGGA, AUGGGC, AUGGGU, AUGGUC, AUGGUG, AUGUAC, AUGUAU, AUGUCA,AUGUCC, AUGUCG, AUGUGU, AUGUUA, AUGUUC, AUUAAA, AUUAAC, AUUAAG, AUUAAU, AUUACA,AUUACC, AUUACG, AUUACU, AUUAGA, AUUAGC, AUUAGG, AUUAGU, AUUAUA, AUUAUC, AUUAUG,AUUCAC, AUUCCA, AUUCCG, AUUCCU, AUUCGA, AUUCGC, AUUCGG, AUUCGU, AUUCUA, AUUCUC,AUUCUU, AUUGAA, AUUGAC, AUUGAU, AUUGCC, AUUGCG, AUUGCU, AUUGGA, AUUGGC,AUUGGG, AUUGGU, AUUGUA, AUUGUC, AUUGUG, AUUGUU, AUUUAA, AUUUAG, AUUUAU,AUUUCC, AUUUCG, AUUUCU, AUUUGA, AUUUGC, AUUUGU, AUUUUA, AUUUUC, AUUUUG,AUUUUU, CAAAAG, CAAACA, CAAACC, CAAACG, CAAACU, CAAAGA, CAAAGG, CAAAUA, CAAAUU,CAACAC, CAACAU, CAACCA, CAACCC, CAACCG, CAACGA, CAACGC, CAACGG, CAACGU, CAACUA,CAACUC, CAACUG, CAACUU, CAAGAA, CAAGAC, CAAGAU, CAAGCA, CAAGCC, CAAGCG, CAAGCU,CAAGGA, CAAGGG, CAAGUC, CAAGUG, CAAGUU, CAAUAA, CAAUAC, CAAUAG, CAAUCC, CAAUCG,CAAUCU, CAAUGA, CAAUGC, CAAUGG, CAAUGU, CAAUUC, CAAUUG, CAAUUU, CACAAU, CACACA,CACACG, CACACU, CACAGA, CACAGC, CACAGG, CACAUA, CACAUC, CACAUU, CACCAA, CACCAC,CACCAU, CACCCA, CACCCC, CACCCG, CACCGA, CACCGC, CACCGG, CACCGU, CACCUA, CACCUU,CACGAA, CACGAC, CACGAG, CACGAU, CACGCA, CACGCC, CACGCU, CACGGA, CACGGC, CACGGG,CACGGU, CACGUA, CACGUC, CACGUG, CACGUU, CACUAA, CACUAG, CACUAU, CACUCA, CACUCG,CACUGA, CACUGC, CACUGG, CACUUA, CACUUC, CACUUU, CAGAAA, CAGAAG, CAGAAU, CAGACC,CAGACG, CAGAGC, CAGAUA, CAGAUC, CAGCCG, CAGCCU, CAGCGA, CAGCGC, CAGCGG, CAGCGU,CAGCUC, CAGCUU, CAGGAU, CAGGGG, CAGGGU, CAGGUA, CAGGUC, CAGGUU, CAGUAC, CAGUCG,CAGUUG, CAUAAA, CAUAAC, CAUAAG, CAUAAU, CAUACA, CAUACC, CAUACG, CAUACU, CAUAGA,CAUAGG, CAUAGU, CAUAUA, CAUAUC, CAUAUG, CAUCAA, CAUCAC, CAUCAG, CAUCAU, CAUCCA,CAUCCC, CAUCCG, CAUCGA, CAUCGC, CAUCGG, CAUCGU, CAUCUA, CAUCUC, CAUCUG, CAUCUU,CAUGAA, CAUGAC, CAUGAG, CAUGAU, CAUGCA, CAUGCC, CAUGCG, CAUGCU, CAUGGC, CAUGGG,CAUGGU, CAUGUA, CAUGUC, CAUGUU, CAUUAA, CAUUAC, CAUUAG, CAUUCA, CAUUCC, CAUUCG,CAUUCU, CAUUGA, CAUUGG, CAUUUC, CAUUUG, CAUUUU, CCAAAA, CCAAAC, CCAAAG, CCAAAU,CCAACA, CCAACC, CCAACG, CCAACU, CCAAGA, CCAAGC, CCAAGG, CCAAUC, CCAAUG, CCAAUU,CCACAA, CCACAC, CCACAG, CCACAU, CCACCA, CCACCC, CCACCG, CCACCU, CCACGA, CCACGC,CCACGG, CCACGU, CCACUA, CCACUC, CCACUU, CCAGAA, CCAGAC, CCAGAG, CCAGCC, CCAGGU,CCAGUC, CCAGUU, CCAUAA, CCAUAC, CCAUAG, CCAUAU, CCAUCA, CCAUCC, CCAUCU, CCAUGA,CCAUGC, CCAUGG, CCAUUC, CCAUUG, CCAUUU, CCCAAC, CCCAAG, CCCAAU, CCCACA, CCCAGA,CCCAGC, CCCAGU, CCCAUA, CCCAUC, CCCAUG, CCCAUU, CCCCAA, CCCCAG, CCCCAU, CCCCCC,CCCCCG, CCCCCU, CCCCGA, CCCCGC, CCCCGU, CCCCUA, CCCCUC, CCCGAA, CCCGAC, CCCGAU,CCCGCA, CCCGCU, CCCGGA, CCCGGC, CCCGUA, CCCGUG, CCCGUU, CCCUAA, CCCUAG, CCCUCA,CCCUCU, CCCUGC, CCCUUA, CCCUUC, CCCUUU, CCGAAA, CCGAAC, CCGAAU, CCGACA, CCGACC,CCGACG, CCGACU, CCGAGA, CCGAGG, CCGAGU, CCGAUA, CCGAUC, CCGAUG, CCGAUU, CCGCAA,CCGCAC, CCGCAG, CCGCAU, CCGCCA, CCGCCC, CCGCCG, CCGCCU, CCGCGA, CCGCGC, CCGCGG,CCGCGU, CCGCUA, CCGCUC, CCGCUG, CCGCUU, CCGGAA, CCGGAU, CCGGCA, CCGGCC, CCGGCG,CCGGCU, CCGGGA, CCGGGC, CCGGGG, CCGGGU, CCGGUA, CCGGUC, CCGGUG, CCGUAA, CCGUAG,CCGUAU, CCGUCA, CCGUCC, CCGUCG, CCGUGA, CCGUGU, CCGUUA, CCGUUC, CCGUUG, CCGUUU,CCUAAC, CCUAAG, CCUAAU, CCUACA, CCUACC, CCUACG, CCUACU, CCUAGA, CCUAGC, CCUAGG,CCUAGU, CCUAUA, CCUAUC, CCUAUG, CCUAUU, CCUCAA, CCUCAC, CCUCAG, CCUCAU, CCUCCA,CCUCCC, CCUCCG, CCUCGA, CCUCGC, CCUCGG, CCUCGU, CCUCUA, CCUCUG, CCUGAC, CCUGAU,CCUGCA, CCUGGG, CCUGGU, CCUGUU, CCUUAA, CCUUAC, CCUUAG, CCUUAU, CCUUCG, CCUUGA,CCUUGU, CCUUUA, CCUUUC, CCUUUU, CGAAAA, CGAAAC, CGAAAG, CGAAAU, CGAACA, CGAACC,CGAACG, CGAACU, CGAAGA, CGAAGC, CGAAGG, CGAAGU, CGAAUA, CGAAUC, CGAAUG, CGAAUU,CGACAA, CGACAC, CGACAU, CGACCA, CGACCU, CGACGA, CGACGC, CGACGG, CGACGU, CGACUA,CGACUG, CGACUU, CGAGAA, CGAGAC, CGAGAG, CGAGAU, CGAGCA, CGAGCC, CGAGCG, CGAGCU,CGAGGC, CGAGGG, CGAGGU, CGAGUA, CGAGUC, CGAGUG, CGAGUU, CGAUAA, CGAUAC, CGAUAG,CGAUAU, CGAUCA, CGAUCC, CGAUCG, CGAUCU, CGAUGA, CGAUGC, CGAUGG, CGAUGU, CGAUUA,CGAUUC, CGAUUG, CGAUUU, CGCAAA, CGCAAC, CGCAAG, CGCAAU, CGCACA, CGCACC, CGCACG,CGCAGA, CGCAGC, CGCAGG, CGCAGU, CGCAUA, CGCAUC, CGCAUG, CGCAUU, CGCCAA, CGCCAC,CGCCAG, CGCCAU, CGCCCA, CGCCCC, CGCCCG, CGCCGA, CGCCGC, CGCCGG, CGCCGU, CGCCUA,CGCCUG, CGCCUU, CGCGAA, CGCGAC, CGCGAG, CGCGAU, CGCGCA, CGCGCC, CGCGCG, CGCGCU,CGCGGA, CGCGGC, CGCGGG, CGCGGU, CGCGUA, CGCGUC, CGCGUG, CGCGUU, CGCUAA, CGCUAC,CGCUAG, CGCUAU, CGCUCA, CGCUCC, CGCUCG, CGCUCU, CGCUGA, CGCUGC, CGCUGG, CGCUGU,CGCUUA, CGCUUC, CGCUUG, CGGAAA, CGGAAC, CGGAAG, CGGACA, CGGACC, CGGACG, CGGACU,CGGAGC, CGGAGG, CGGAGU, CGGAUA, CGGAUU, CGGCAA, CGGCAC, CGGCAG, CGGCCA, CGGCCC,CGGCCG, CGGCGC, CGGCGG, CGGCGU, CGGCUA, CGGCUC, CGGCUG, CGGCUU, CGGGAA, CGGGAC,CGGGAG, CGGGAU, CGGGCA, CGGGCC, CGGGCG, CGGGCU, CGGGGU, CGGGUA, CGGGUC, CGGGUG,CGGUAA, CGGUAC, CGGUAG, CGGUAU, CGGUCA, CGGUCG, CGGUCU, CGGUGA, CGGUGG, CGGUGU,CGGUUA, CGGUUC, CGGUUG, CGGUUU, CGUAAA, CGUAAC, CGUAAG, CGUAAU, CGUACA, CGUACG,CGUACU, CGUAGA, CGUAGC, CGUAGG, CGUAGU, CGUAUA, CGUAUC, CGUAUG, CGUAUU, CGUCAA,CGUCAC, CGUCAG, CGUCAU, CGUCCA, CGUCCC, CGUCCG, CGUCCU, CGUCGA, CGUCGG, CGUCGU,CGUCUA, CGUCUC, CGUCUG, CGUCUU, CGUGAA, CGUGAC, CGUGAG, CGUGAU, CGUGCC, CGUGCG,CGUGCU, CGUGGA, CGUGGG, CGUGGU, CGUGUA, CGUGUG, CGUUAA, CGUUAC, CGUUAG,CGUUAU, CGUUCA, CGUUCC, CGUUCG, CGUUCU, CGUUGA, CGUUGC, CGUUGU, CGUUUA, CGUUUC,CGUUUU, CUAAAA, CUAAAC, CUAAAU, CUAACA, CUAACC, CUAACG, CUAACU, CUAAGA, CUAAGC,CUAAGU, CUAAUA, CUAAUC, CUAAUG, CUACAC, CUACAU, CUACCA, CUACCC, CUACCG, CUACCU,CUACGA, CUACGC, CUACGG, CUACGU, CUACUA, CUACUC, CUACUG, CUAGAA, CUAGAG, CUAGAU,CUAGCA, CUAGCC, CUAGCG, CUAGCU, CUAGGA, CUAGGG, CUAGGU, CUAGUG, CUAGUU, CUAUAA,CUAUAG, CUAUAU, CUAUCA, CUAUCC, CUAUCG, CUAUCU, CUAUGA, CUAUGC, CUAUGG, CUAUGU,CUAUUA, CUAUUG, CUCAAC, CUCAAG, CUCAAU, CUCACC, CUCACG, CUCAGC, CUCAUA, CUCAUC,CUCAUG, CUCAUU, CUCCAC, CUCCCC, CUCCCG, CUCCGA, CUCCGC, CUCCGG, CUCCUA, CUCCUC,CUCCUU, CUCGAA, CUCGAC, CUCGAG, CUCGAU, CUCGCA, CUCGCC, CUCGCG, CUCGGG, CUCGGU,CUCGUA, CUCGUC, CUCGUG, CUCGUU, CUCUAA, CUCUAC, CUCUAU, CUCUCA, CUCUCC, CUCUCU,CUCUGC, CUCUGU, CUCUUA, CUCUUG, CUGAAG, CUGACC, CUGACG, CUGAGC, CUGAUA, CUGAUC,CUGCCG, CUGCCU, CUGCGA, CUGCUA, CUGCUU, CUGGAG, CUGGAU, CUGGCG, CUGGGU, CUGUAC,CUGUCA, CUGUCC, CUGUCG, CUGUGG, CUGUGU, CUGUUA, CUGUUU, CUUAAC, CUUAAG, CUUAAU,CUUACC, CUUACG, CUUAGA, CUUAGC, CUUAGG, CUUAGU, CUUAUA, CUUAUC, CUUAUG, CUUAUU,CUUCAG, CUUCAU, CUUCCA, CUUCCC, CUUCCG, CUUCCU, CUUCGA, CUUCGC, CUUCGG, CUUCGU,CUUCUA, CUUGAC, CUUGAG, CUUGAU, CUUGCA, CUUGCC, CUUGCG, CUUGCU, CUUGGC, CUUGGU,CUUGUU, CUUUAC, CUUUAG, CUUUAU, CUUUCA, CUUUCG, CUUUCU, CUUUGA, CUUUGC, CUUUGU,CUUUUA, CUUUUC, CUUUUG, CUUUUU, GAAAAA, GAAAAG, GAAAAU, GAAACC, GAAACG, GAAAGA,GAAAGC, GAAAGU, GAAAUA, GAAAUC, GAAAUG, GAAAUU, GAACAA, GAACAC, GAACAG, GAACAU,GAACCA, GAACCC, GAACCG, GAACCU, GAACGA, GAACGC, GAACGG, GAACGU, GAACUA, GAACUG,GAACUU, GAAGAC, GAAGAG, GAAGCA, GAAGCG, GAAGCU, GAAGUC, GAAUAA, GAAUAC, GAAUAG,GAAUAU, GAAUCC, GAAUCG, GAAUCU, GAAUGA, GAAUGC, GAAUGU, GAAUUA, GAAUUC, GAAUUU,GACAAA, GACAAG, GACAAU, GACACC, GACAGA, GACAGG, GACAUA, GACAUG, GACAUU, GACCAA,GACCAC, GACCAG, GACCCA, GACCCC, GACCCG, GACCGC, GACCGG, GACCGU, GACCUA, GACCUC,GACCUU, GACGAA, GACGAC, GACGAG, GACGAU, GACGCA, GACGCC, GACGCG, GACGCU, GACGGA,GACGGC, GACGGG, GACGGU, GACGUA, GACGUC, GACGUG, GACGUU, GACUAA, GACUAC, GACUAG,GACUAU, GACUCA, GACUCC, GACUCG, GACUGG, GACUGU, GACUUA, GACUUG, GACUUU, GAGAAU,GAGAGA, GAGAGC, GAGAGG, GAGAUA, GAGAUC, GAGCAA, GAGCAU, GAGCCA, GAGCGA, GAGCGG,GAGCGU, GAGGGU, GAGGUC, GAGGUG, GAGUAA, GAGUAG, GAGUCC, GAGUUC, GAGUUU,GAUAAA, GAUAAC, GAUAAG, GAUAAU, GAUACA, GAUACC, GAUACG, GAUACU, GAUAGA, GAUAGC,GAUAGG, GAUAGU, GAUAUA, GAUCAA, GAUCAC, GAUCAU, GAUCCA, GAUCCC, GAUCCU, GAUCGC,GAUCGG, GAUCGU, GAUCUA, GAUCUG, GAUCUU, GAUGAA, GAUGAC, GAUGAG, GAUGCA, GAUGCC,GAUGCG, GAUGCU, GAUGGC, GAUGGG, GAUGGU, GAUGUG, GAUGUU, GAUUAA, GAUUAC,GAUUAG, GAUUAU, GAUUCA, GAUUCG, GAUUCU, GAUUGA, GAUUGC, GAUUUA, GAUUUC,GAUUUG, GAUUUU, GCAAAC, GCAAAG, GCAAAU, GCAACA, GCAACC, GCAAGC, GCAAGU, GCAAUA,GCAAUC, GCAAUG, GCAAUU, GCACAA, GCACAC, GCACAG, GCACCC, GCACCG, GCACCU, GCACGA,GCACGC, GCACGU, GCACUA, GCACUC, GCACUG, GCACUU, GCAGAU, GCAGCC, GCAGCG, GCAGGC,GCAGUA, GCAGUC, GCAGUG, GCAGUU, GCAUAA, GCAUAG, GCAUAU, GCAUCG, GCAUCU, GCAUGA,GCAUGC, GCAUGG, GCAUGU, GCAUUA, GCAUUC, GCAUUG, GCAUUU, GCCAAA, GCCAAC, GCCAAU,GCCACA, GCCACC, GCCACG, GCCAGA, GCCAGU, GCCAUA, GCCAUC, GCCAUG, GCCAUU, GCCCAA,GCCCAC, GCCCAG, GCCCCG, GCCCGA, GCCCGG, GCCCGU, GCCGAA, GCCGAC, GCCGAG, GCCGAU,GCCGCA, GCCGCU, GCCGGA, GCCGGC, GCCGGG, GCCGGU, GCCGUA, GCCGUC, GCCGUG, GCCGUU,GCCUAA, GCCUAU, GCCUCA, GCCUCC, GCCUCG, GCCUGA, GCCUUA, GCCUUU, GCGAAA, GCGAAC,GCGAAG, GCGAAU, GCGACC, GCGACG, GCGACU, GCGAGA, GCGAGC, GCGAGG, GCGAGU, GCGAUA,GCGAUC, GCGAUG, GCGAUU, GCGCAA, GCGCAC, GCGCAG, GCGCAU, GCGCCA, GCGCCC, GCGCCU,GCGCGA, GCGCGU, GCGCUA, GCGCUC, GCGCUG, GCGCUU, GCGGAA, GCGGAC, GCGGAU, GCGGCA,GCGGCC, GCGGCU, GCGGGA, GCGGUA, GCGGUC, GCGGUU, GCGUAA, GCGUAC, GCGUAG, GCGUAU,GCGUCA, GCGUCC, GCGUCG, GCGUCU, GCGUGA, GCGUGC, GCGUGG, GCGUGU, GCGUUA, GCGUUC,GCGUUG, GCGUUU, GCUAAA, GCUAAC, GCUAAG, GCUAAU, GCUACC, GCUACG, GCUACU, GCUAGA,GCUAGG, GCUAGU, GCUAUA, GCUAUC, GCUAUU, GCUCAA, GCUCAC, GCUCAG, GCUCAU, GCUCCA,GCUCCC, GCUCCG, GCUCGA, GCUCGC, GCUCGU, GCUCUA, GCUCUC, GCUCUU, GCUGAA, GCUGAC,GCUGAU, GCUGCA, GCUGCC, GCUGCG, GCUGCU, GCUGUG, GCUGUU, GCUUAC, GCUUAG, GCUUAU,GCUUCA, GCUUCG, GCUUGA, GCUUGG, GCUUGU, GCUUUA, GCUUUG, GGAAAG, GGAACA, GGAACC,GGAACG, GGAACU, GGAAGU, GGAAUA, GGAAUC, GGAAUU, GGACAA, GGACAC, GGACAG, GGACAU,GGACCG, GGACGA, GGACGC, GGACGU, GGACUA, GGACUC, GGACUU, GGAGAC, GGAGCA, GGAGCG,GGAGGG, GGAGUA, GGAUAA, GGAUAC, GGAUCA, GGAUCC, GGAUCG, GGAUCU, GGAUGC, GGAUUA,GGAUUG, GGCAAU, GGCACA, GGCACU, GGCAGA, GGCAUA, GGCAUC, GGCCAC, GGCCAG, GGCCCC,GGCCGA, GGCCGC, GGCCGU, GGCCUA, GGCCUG, GGCCUU, GGCGAA, GGCGAG, GGCGAU, GGCGCA,GGCGCU, GGCGGU, GGCGUA, GGCGUC, GGCGUG, GGCGUU, GGCUAA, GGCUAC, GGCUAG, GGCUAU,GGCUCC, GGCUCG, GGCUGA, GGCUUA, GGCUUC, GGCUUG, GGGAAU, GGGACA, GGGAGA, GGGAGU,GGGAUA, GGGAUU, GGGCAA, GGGCAC, GGGCAG, GGGCCG, GGGCGG, GGGGCC, GGGGGG,GGGGGU, GGGGUA, GGGUAC, GGGUAU, GGGUCA, GGGUCC, GGGUCG, GGGUGA, GGGUGC,GGGUUA, GGGUUG, GGUAAA, GGUAAC, GGUAAG, GGUAAU, GGUACA, GGUACC, GGUACG,GGUACU, GGUAGC, GGUAGG, GGUAGU, GGUAUA, GGUAUC, GGUAUG, GGUCAA, GGUCAC,GGUCAG, GGUCAU, GGUCCA, GGUCCG, GGUCCU, GGUCGA, GGUCGC, GGUCGG, GGUCGU, GGUCUC,GGUCUU, GGUGAA, GGUGAC, GGUGAU, GGUGCA, GGUGCC, GGUGGC, GGUGUA, GGUGUC,GGUUAA, GGUUAG, GGUUAU, GGUUCA, GGUUCC, GGUUCG, GGUUGC, GGUUUC, GGUUUU,GUAAAA, GUAAAG, GUAAAU, GUAACC, GUAACG, GUAACU, GUAAGA, GUAAGC, GUAAGG, GUAAGU,GUAAUA, GUAAUC, GUAAUG, GUAAUU, GUACAA, GUACAC, GUACAG, GUACAU, GUACCA, GUACCC,GUACCG, GUACCU, GUACGA, GUACGC, GUACGG, GUACGU, GUACUA, GUACUC, GUACUG, GUACUU,GUAGAA, GUAGAC, GUAGCA, GUAGCC, GUAGCG, GUAGCU, GUAGGA, GUAGGC, GUAGGG,GUAGGU, GUAGUA, GUAGUC, GUAUAA, GUAUAC, GUAUAG, GUAUAU, GUAUCA, GUAUCG,GUAUCU, GUAUGA, GUAUGC, GUAUGG, GUAUUA, GUAUUG, GUAUUU, GUCAAA, GUCAAG,GUCAAU, GUCACA, GUCACC, GUCACG, GUCAGA, GUCAGC, GUCAGG, GUCAUA, GUCAUC, GUCAUG,GUCCAA, GUCCAC, GUCCAU, GUCCCC, GUCCCU, GUCCGA, GUCCGC, GUCCGG, GUCCGU, GUCCUA,GUCCUG, GUCCUU, GUCGAA, GUCGAC, GUCGAG, GUCGAU, GUCGCA, GUCGCC, GUCGCG, GUCGCU,GUCGGA, GUCGGC, GUCGGG, GUCGGU, GUCGUA, GUCGUC, GUCGUU, GUCUAA, GUCUAG, GUCUCA,GUCUCC, GUCUCG, GUCUGA, GUCUGG, GUCUGU, GUCUUC, GUCUUU, GUGAAA, GUGAAC, GUGAAG,GUGACC, GUGACG, GUGAGA, GUGAGC, GUGAGU, GUGAUC, GUGAUG, GUGAUU, GUGCAC,GUGCAU, GUGCCC, GUGCCG, GUGCGA, GUGCGG, GUGCGU, GUGCUA, GUGCUC, GUGCUG,GUGGAG, GUGGCG, GUGGCU, GUGGGU, GUGGUC, GUGGUG, GUGUAA, GUGUAG, GUGUCG,GUGUGA, GUGUGC, GUGUGU, GUGUUG, GUGUUU, GUUAAA, GUUAAC, GUUAAG, GUUACA,GUUACC, GUUACG, GUUACU, GUUAGA, GUUAGC, GUUAGU, GUUAUA, GUUAUC, GUUAUG,GUUAUU, GUUCAA, GUUCAC, GUUCAG, GUUCCA, GUUCCG, GUUCGA, GUUCGC, GUUCGG, GUUCGU,GUUCUA, GUUCUG, GUUGAA, GUUGAC, GUUGAG, GUUGAU, GUUGCG, GUUGCU, GUUGGA,GUUGGC, GUUGGU, GUUGUC, GUUGUG, GUUGUU, GUUUAA, GUUUAC, GUUUAG, GUUUAU,GUUUCA, GUUUCC, GUUUCU, GUUUGA, GUUUGC, GUUUGG, GUUUGU, GUUUUA, GUUUUC,GUUUUU, UAAAAA, UAAAAC, UAAAAG, UAAAAU, UAAACA, UAAACC, UAAACG, UAAACU, UAAAGA,UAAAGG, UAAAGU, UAAAUA, UAAAUC, UAAAUG, UAAAUU, UAACAA, UAACAC, UAACAG, UAACCA,UAACCC, UAACCG, UAACCU, UAACGA, UAACGC, UAACGG, UAACGU, UAACUA, UAACUG, UAACUU,UAAGAG, UAAGAU, UAAGCA, UAAGCC, UAAGCG, UAAGCU, UAAGGA, UAAGGC, UAAGGG, UAAGGU,UAAGUA, UAAGUC, UAAGUG, UAAGUU, UAAUAA, UAAUCA, UAAUCC, UAAUCG, UAAUCU, UAAUGA,UAAUGG, UAAUGU, UAAUUA, UAAUUC, UAAUUG, UACAAC, UACAAG, UACAAU, UACACC, UACACG,UACACU, UACAGA, UACAGC, UACAUA, UACAUC, UACAUU, UACCAA, UACCAC, UACCAG, UACCAU,UACCCC, UACCCG, UACCCU, UACCGA, UACCGC, UACCGG, UACCGU, UACCUA, UACCUG, UACGAA,UACGAC, UACGAG, UACGAU, UACGCA, UACGCC, UACGCG, UACGCU, UACGGC, UACGGG, UACGGU,UACGUA, UACGUC, UACGUG, UACGUU, UACUAA, UACUAC, UACUAG, UACUAU, UACUCA, UACUCC,UACUCG, UACUCU, UACUGA, UACUGC, UACUGG, UACUUA, UACUUG, UACUUU, UAGAAA, UAGAAG,UAGAAU, UAGACA, UAGACG, UAGAGA, UAGAGC, UAGAGU, UAGAUA, UAGAUC, UAGAUG, UAGCAU,UAGCCC, UAGCCG, UAGCCU, UAGCGA, UAGCGC, UAGCGU, UAGCUA, UAGCUC, UAGCUG, UAGGAA,UAGGAU, UAGGCG, UAGGCU, UAGGGU, UAGGUC, UAGGUG, UAGGUU, UAGUAA, UAGUAC,UAGUAG, UAGUAU, UAGUCA, UAGUCG, UAGUGU, UAGUUA, UAGUUC, UAGUUG, UAGUUU,UAUAAC, UAUAAG, UAUACU, UAUAGA, UAUAGC, UAUAGG, UAUAGU, UAUAUA, UAUAUC, UAUAUG,UAUAUU, UAUCAA, UAUCAC, UAUCAU, UAUCCA, UAUCCC, UAUCCG, UAUCCU, UAUCGA, UAUCGC,UAUCGG, UAUCGU, UAUCUA, UAUCUC, UAUCUG, UAUCUU, UAUGAA, UAUGAC, UAUGAG,UAUGAU, UAUGCA, UAUGCG, UAUGCU, UAUGGA, UAUGGC, UAUGUC, UAUGUG, UAUGUU,UAUUAG, UAUUCA, UAUUCC, UAUUCG, UAUUCU, UAUUGA, UAUUGG, UAUUUA, UAUUUC,UAUUUG, UAUUUU, UCAAAA, UCAAAC, UCAAAG, UCAACC, UCAACU, UCAAGA, UCAAGC, UCAAUA,UCAAUC, UCAAUG, UCAAUU, UCACCC, UCACCG, UCACCU, UCACGA, UCACGC, UCACGG, UCACGU,UCACUA, UCACUC, UCACUU, UCAGAA, UCAGAC, UCAGAG, UCAGCG, UCAGCU, UCAGGA, UCAGGC,UCAGGU, UCAGUC, UCAGUU, UCAUAA, UCAUCA, UCAUCC, UCAUCG, UCAUGC, UCAUGG, UCAUGU,UCAUUA, UCAUUG, UCCAAA, UCCAAC, UCCAAG, UCCAAU, UCCACA, UCCACC, UCCACG, UCCAGC,UCCAGG, UCCAUA, UCCAUC, UCCAUU, UCCCAA, UCCCAG, UCCCAU, UCCCCC, UCCCCG, UCCCCU,UCCCGA, UCCCGC, UCCCGG, UCCCGU, UCCCUA, UCCCUC, UCCGAA, UCCGAC, UCCGAG, UCCGAU,UCCGCA, UCCGCC, UCCGGA, UCCGGC, UCCGGU, UCCGUA, UCCGUC, UCCGUG, UCCUAA, UCCUCA,UCCUCG, UCCUCU, UCCUGC, UCCUGU, UCCUUA, UCCUUC, UCCUUU, UCGAAA, UCGAAC, UCGAAG,UCGAAU, UCGACA, UCGACC, UCGACG, UCGACU, UCGAGA, UCGAGC, UCGAGG, UCGAUA, UCGAUC,UCGAUG, UCGAUU, UCGCAA, UCGCAC, UCGCAG, UCGCAU, UCGCCA, UCGCCC, UCGCCG, UCGCCU,UCGCGA, UCGCGC, UCGCGU, UCGCUA, UCGCUC, UCGGAA, UCGGAC, UCGGAG, UCGGAU, UCGGCA,UCGGCU, UCGGGG, UCGGGU, UCGGUC, UCGGUG, UCGGUU, UCGUAA, UCGUAC, UCGUAG,UCGUAU, UCGUCA, UCGUCC, UCGUCG, UCGUCU, UCGUGA, UCGUGU, UCGUUA, UCGUUC, UCGUUG,UCGUUU, UCUAAC, UCUAAG, UCUAAU, UCUACA, UCUACC, UCUACG, UCUACU, UCUAGC, UCUAGG,UCUAGU, UCUAUA, UCUAUC, UCUAUG, UCUAUU, UCUCAG, UCUCAU, UCUCCG, UCUCGC, UCUCGG,UCUCGU, UCUCUC, UCUGAA, UCUGAU, UCUGCA, UCUGCG, UCUGCU, UCUGGC, UCUGGU, UCUGUC,UCUGUG, UCUGUU, UCUUAA, UCUUAC, UCUUAG, UCUUAU, UCUUCA, UCUUCC, UCUUCG, UCUUCU,UCUUGC, UCUUGG, UCUUGU, UCUUUA, UCUUUC, UCUUUG, UCUUUU, UGAAAA, UGAAAC,UGAACA, UGAACC, UGAAGG, UGAAUC, UGAAUG, UGACAA, UGACAC, UGACAG, UGACCA, UGACCC,UGACCG, UGACGA, UGACGC, UGACGG, UGACGU, UGACUA, UGACUC, UGACUU, UGAGAG, UGAGAU,UGAGCA, UGAGCC, UGAGCU, UGAGGC, UGAGGU, UGAGUA, UGAGUU, UGAUAC, UGAUAG,UGAUAU, UGAUCA, UGAUCG, UGAUCU, UGAUGA, UGAUGC, UGAUGG, UGAUGU, UGAUUA,UGAUUC, UGAUUG, UGAUUU, UGCAAC, UGCAAG, UGCACA, UGCACG, UGCAGG, UGCAGU, UGCAUC,UGCCCA, UGCCCC, UGCCCG, UGCCGA, UGCCGC, UGCCGG, UGCCGU, UGCCUA, UGCCUC, UGCCUG,UGCCUU, UGCGAA, UGCGAC, UGCGAU, UGCGCC, UGCGCG, UGCGCU, UGCGGC, UGCGGG, UGCGGU,UGCGUA, UGCGUC, UGCGUG, UGCGUU, UGCUAC, UGCUAU, UGCUCC, UGCUCG, UGCUGC, UGCUGG,UGCUGU, UGCUUA, UGCUUU, UGGAAC, UGGAAG, UGGAGC, UGGAUC, UGGAUU, UGGCAA,UGGCAC, UGGCAG, UGGCCG, UGGCCU, UGGCGA, UGGCGC, UGGCGU, UGGCUA, UGGCUC, UGGCUU,UGGGAA, UGGGCA, UGGGCC, UGGGGC, UGGGUC, UGGUAA, UGGUAG, UGGUAU, UGGUCC,UGGUCG, UGGUCU, UGGUGA, UGGUGC, UGGUGG, UGGUGU, UGGUUA, UGGUUG, UGUAAA,UGUAAC, UGUAAG, UGUACC, UGUACG, UGUACU, UGUAGA, UGUAGC, UGUAGU, UGUAUC,UGUAUU, UGUCAA, UGUCAC, UGUCAG, UGUCAU, UGUCCA, UGUCCC, UGUCCG, UGUCGA, UGUCGC,UGUCGG, UGUCGU, UGUCUA, UGUCUC, UGUGAC, UGUGAG, UGUGAU, UGUGCA, UGUGGU,UGUGUA, UGUGUU, UGUUAC, UGUUAG, UGUUAU, UGUUCA, UGUUCC, UGUUCG, UGUUGG,UGUUGU, UGUUUA, UGUUUC, UGUUUG, UGUUUU, UUAAAA, UUAAAC, UUAAAG, UUAAAU,UUAACC, UUAACG, UUAACU, UUAAGU, UUAAUA, UUAAUC, UUAAUG, UUAAUU, UUACAA, UUACAC,UUACAG, UUACAU, UUACCA, UUACCC, UUACCG, UUACCU, UUACGA, UUACGC, UUACGG, UUACGU,UUACUA, UUACUC, UUACUG, UUACUU, UUAGAA, UUAGAC, UUAGCC, UUAGCG, UUAGCU, UUAGGC,UUAGGU, UUAGUA, UUAGUC, UUAGUU, UUAUAA, UUAUAC, UUAUAG, UUAUAU, UUAUCC,UUAUCG, UUAUCU, UUAUGA, UUAUGG, UUAUGU, UUAUUA, UUAUUC, UUAUUG, UUAUUU,UUCAAC, UUCAAU, UUCACA, UUCACC, UUCACG, UUCACU, UUCAGC, UUCAGG, UUCAGU, UUCAUA,UUCAUC, UUCAUG, UUCAUU, UUCCAA, UUCCCA, UUCCCG, UUCCGA, UUCCGU, UUCCUU, UUCGAA,UUCGAC, UUCGAG, UUCGAU, UUCGCA, UUCGCC, UUCGCG, UUCGCU, UUCGGA, UUCGGC, UUCGGG,UUCGGU, UUCGUA, UUCGUC, UUCGUG, UUCGUU, UUCUAC, UUCUAG, UUCUCA, UUCUCG,UUCUGG, UUCUUA, UUCUUU, UUGAAA, UUGAAC, UUGAAG, UUGAAU, UUGACC, UUGACG,UUGACU, UUGAGA, UUGAGC, UUGAGU, UUGAUA, UUGAUC, UUGAUG, UUGAUU, UUGCAA,UUGCAC, UUGCAG, UUGCAU, UUGCCC, UUGCCG, UUGCGA, UUGCGC, UUGCGG, UUGCGU, UUGCUA,UUGCUC, UUGCUG, UUGCUU, UUGGAA, UUGGAG, UUGGCC, UUGGCG, UUGGCU, UUGGGC,UUGGGU, UUGGUA, UUGGUG, UUGUAA, UUGUAC, UUGUCA, UUGUCG, UUGUCU, UUGUGC,UUGUGG, UUGUUA, UUGUUG, UUGUUU, UUUAAA, UUUAAC, UUUAAG, UUUAAU, UUUACA,UUUACC, UUUACG, UUUACU, UUUAGA, UUUAGC, UUUAGG, UUUAGU, UUUAUA, UUUAUC,UUUAUG, UUUAUU, UUUCAU, UUUCCA, UUUCCG, UUUCCU, UUUCGA, UUUCGC, UUUCGG,UUUCGU, UUUCUA, UUUCUC, UUUCUG, UUUCUU, UUUGAA, UUUGAC, UUUGAG, UUUGAU,UUUGCC, UUUGCU, UUUGGA, UUUGGC, UUUGGG, UUUGGU, UUUGUA, UUUGUC, UUUGUU,UUUUAA, UUUUAG, UUUUAU, UUUUCC, UUUUCG, UUUUCU, UUUUGA, UUUUGC, UUUUGG,UUUUGU, UUUUUA, UUUUUC, UUUUUU

TABLE 2 Oligonucleotide sequences made for testing. Oligo cell TimeAssay SeqID Name Avg RQ Avg RQ SE Expt # Target [oligo] line (hr) Type313770 UTRN- 0.56722359 0.19874762 1092 UTRN- 10000 HSKM 240 qRTPCR 01m01 69 5776 UTRN- 0.67184319 0.02092561 1092 UTRN- 10000 HSKM 240 qRTPCR02 m01 69 5781 UTRN- 0.67120255 0.02923406 1092 UTRN- 10000 HSKM 240qRTPCR 03 m01 69 32192 UTRN- 0.47381841 0.07845869 1092 UTRN- 10000 HSKM240 qRTPCR 04 m01 69 39558 UTRN- 0.37910782 0.01099078 1092 UTRN- 10000HSKM 240 qRTPCR 05 m01 69 45784 UTRN- 0.57173237 0.07542375 1092 UTRN-10000 HSKM 240 qRTPCR 06 m01 69 60002 UTRN- 0.81935385 0.2957031 1092UTRN- 10000 HSKM 240 qRTPCR 07 m01 69 60035 UTRN- 0.47643682 0.009562361092 UTRN- 10000 HSKM 240 qRTPCR 08 m01 69 60038 UTRN- 0.276416680.02978163 1092 UTRN- 10000 HSKM 240 qRTPCR 09 m01 69 336679 UTRN-0.4548524 0.04438911 1092 UTRN- 10000 HSKM 240 qRTPCR 10 m01 69 62709UTRN- 0.31515099 0.08650396 1092 UTRN- 10000 HSKM 240 qRTPCR 11 m01 6964394 UTRN- 0.33957971 0.07934133 1092 UTRN- 10000 HSKM 240 qRTPCR 12m01 69 64407 UTRN- 0.48259158 0.02130792 1092 UTRN- 10000 HSKM 240qRTPCR 13 m01 69 68368 UTRN- 0.5186531 0.04635273 1092 UTRN- 10000 HSKM240 qRTPCR 14 m01 69 68420 UTRN- 0.40961743 0.01198532 1092 UTRN- 10000HSKM 240 qRTPCR 15 m01 69 68424 UTRN- 0.58260161 0.08279854 1092 UTRN-10000 HSKM 240 qRTPCR 16 m01 69 225662 UTRN- 0.40878698 0.0396697 1092UTRN- 10000 HSKM 240 qRTPCR 51 m01 69 229456 UTRN- 0.52805355 0.092710421092 UTRN- 10000 HSKM 240 qRTPCR 52 m01 69 436557 UTRN- 0.604869340.01210078 1092 UTRN- 10000 HSKM 240 qRTPCR 53 m01 69 238467 UTRN-0.48843878 0.08898362 1092 UTRN- 10000 HSKM 240 qRTPCR 54 m01 69 242264UTRN- 0.44606685 0.11570192 1092 UTRN- 10000 HSKM 240 qRTPCR 55 m01 69251939 UTRN- 0.62479703 0.10459768 1092 UTRN- 10000 HSKM 240 qRTPCR 56m01 69 453443 UTRN- 0.62712277 0.10181988 1092 UTRN- 10000 HSKM 240qRTPCR 57 m01 69 453483 UTRN- 0.60355641 0.06283768 1092 UTRN- 10000HSKM 240 qRTPCR 58 m01 69 456038 UTRN- 0.55331257 0.00333395 1092 UTRN-10000 HSKM 240 qRTPCR 59 m01 69 272301 UTRN- 0.68004552 0.04014439 1092UTRN- 10000 HSKM 240 qRTPCR 60 m01 69 276749 UTRN- 0.40554491 0.044284041092 UTRN- 10000 HSKM 240 qRTPCR 61 m01 69 289697 UTRN- 0.575474050.10918106 1092 UTRN- 10000 HSKM 240 qRTPCR 62 m01 69 292490 UTRN-1.22451016 0.1400616 1092 UTRN- 10000 HSKM 240 qRTPCR 63 m01 69 292535UTRN- 0.35813772 0.02632312 1092 UTRN- 10000 HSKM 240 qRTPCR 64 m01 69292541 UTRN- 0.5783448 0.14263157 1092 UTRN- 10000 HSKM 240 qRTPCR 65m01 69 Ctrl Un 1 0.15624566 1092 UTRN- 10000 HSKM 240 qRTPCR 69 313770UTRN- 0.80889119 0.22465479 1092 UTRN- 10000 HSKM 240 qRTPCR 01 m01 025776 UTRN- 0.40448717 0.06346895 1092 UTRN- 10000 HSKM 240 qRTPCR 02 m0102 5781 UTRN- 0.42883333 0.01903559 1092 UTRN- 10000 HSKM 240 qRTPCR 03m01 02 32192 UTRN- 0.58600693 0.04983107 1092 UTRN- 10000 HSKM 240qRTPCR 04 m01 02 39558 UTRN- 0.44668903 0.03733429 1092 UTRN- 10000 HSKM240 qRTPCR 05 m01 02 45784 UTRN- 0.60263964 0.05898416 1092 UTRN- 10000HSKM 240 qRTPCR 06 m01 02 60002 UTRN- 0.65881688 0.15865717 1092 UTRN-10000 HSKM 240 qRTPCR 07 m01 02 60035 UTRN- 0.45969974 0.02226413 1092UTRN- 10000 HSKM 240 qRTPCR 08 m01 02 60038 UTRN- 0.28578991 0.053865351092 UTRN- 10000 HSKM 240 qRTPCR 09 m01 02 336679 UTRN- 0.425173890.07119164 1092 UTRN- 10000 HSKM 240 qRTPCR 10 m01 02 62709 UTRN-0.26632703 0.08404946 1092 UTRN- 10000 HSKM 240 qRTPCR 11 m01 02 64394UTRN- 0.24238335 0.08508889 1092 UTRN- 10000 HSKM 240 qRTPCR 12 m01 0264407 UTRN- 0.3867596 0.02251739 1092 UTRN- 10000 HSKM 240 qRTPCR 13 m0102 68368 UTRN- 0.5047263 0.06510318 1092 UTRN- 10000 HSKM 240 qRTPCR 14m01 02 68420 UTRN- 0.35145444 0.00360596 1092 UTRN- 10000 HSKM 240qRTPCR 15 m01 02 68424 UTRN- 0.25078544 0.0448786 1092 UTRN- 10000 HSKM240 qRTPCR 16 m01 02 225662 UTRN- 0.42594611 0.01741836 1092 UTRN- 10000HSKM 240 qRTPCR 51 m01 02 229456 UTRN- 0.45785694 0.0993462 1092 UTRN-10000 HSKM 240 qRTPCR 52 m01 02 436557 UTRN- 0.52935015 0.07073485 1092UTRN- 10000 HSKM 240 qRTPCR 53 m01 02 238467 UTRN- 0.38557612 0.103925751092 UTRN- 10000 HSKM 240 qRTPCR 54 m01 02 242264 UTRN- 0.385395740.08982757 1092 UTRN- 10000 HSKM 240 qRTPCR 55 m01 02 251939 UTRN-0.5275769 0.07069548 1092 UTRN- 10000 HSKM 240 qRTPCR 56 m01 02 453443UTRN- 0.60576249 0.08631879 1092 UTRN- 10000 HSKM 240 qRTPCR 57 m01 02453483 UTRN- 1.16594129 0.207295 1092 UTRN- 10000 HSKM 240 qRTPCR 58 m0102 456038 UTRN- 0.74009641 0.06482759 1092 UTRN- 10000 HSKM 240 qRTPCR59 m01 02 272301 UTRN- 0.56858603 0.01375065 1092 UTRN- 10000 HSKM 240qRTPCR 60 m01 02 276749 UTRN- 0.34556947 0.01341551 1092 UTRN- 10000HSKM 240 qRTPCR 61 m01 02 289697 UTRN- 0.57219193 0.11079267 1092 UTRN-10000 HSKM 240 qRTPCR 62 m01 02 292490 UTRN- 1.76162269 0.37735928 1092UTRN- 10000 HSKM 240 qRTPCR 63 m01 02 292535 UTRN- 0.42586244 0.134291092 UTRN- 10000 HSKM 240 qRTPCR 64 m01 02 292541 UTRN- 0.492575320.18416443 1092 UTRN- 10000 HSKM 240 qRTPCR 65 m01 02 Ctrl Un 10.12734144 1092 UTRN- 10000 HSKM 240 qRTPCR 02 313770 UTRN- 0.673623390.2232522 1092 UTRN- 10000 HSKM 240 qRTPCR 01 m01 16 5776 UTRN-0.59489089 0.01623233 1092 UTRN- 10000 HSKM 240 qRTPCR 02 m01 16 5781UTRN- 0.60756352 0.02120997 1092 UTRN- 10000 HSKM 240 qRTPCR 03 m01 1632192 UTRN- 0.84579108 0.07082459 1092 UTRN- 10000 HSKM 240 qRTPCR 04m01 16 39558 UTRN- 0.52590671 0.02640074 1092 UTRN- 10000 HSKM 240qRTPCR 05 m01 16 45784 UTRN- 0.55979289 0.09669573 1092 UTRN- 10000 HSKM240 qRTPCR 06 m01 16 60002 UTRN- 0.82437207 0.13621597 1092 UTRN- 10000HSKM 240 qRTPCR 07 m01 16 60035 UTRN- 1.02069162 0.15643042 1092 UTRN-10000 HSKM 240 qRTPCR 08 m01 16 60038 UTRN- 0.52400801 0.11892967 1092UTRN- 10000 HSKM 240 qRTPCR 09 m01 16 336679 UTRN- 0.66653372 0.005786351092 UTRN- 10000 HSKM 240 qRTPCR 10 m01 16 62709 UTRN- 0.464890430.11377591 1092 UTRN- 10000 HSKM 240 qRTPCR 11 m01 16 64394 UTRN-0.29381633 0.10236692 1092 UTRN- 10000 HSKM 240 qRTPCR 12 m01 16 64407UTRN- 0.43332498 0.02180279 1092 UTRN- 10000 HSKM 240 qRTPCR 13 m01 1668368 UTRN- 0.60192704 0.07793789 1092 UTRN- 10000 HSKM 240 qRTPCR 14m01 16 68420 UTRN- 0.50850314 0.02026773 1092 UTRN- 10000 HSKM 240qRTPCR 15 m01 16 68424 UTRN- 0.79338782 0.14011627 1092 UTRN- 10000 HSKM240 qRTPCR 16 m01 16 225662 UTRN- 0.61828072 0.03135995 1092 UTRN- 10000HSKM 240 qRTPCR 51 m01 16 229456 UTRN- 0.67684173 0.11544636 1092 UTRN-10000 HSKM 240 qRTPCR 52 m01 16 436557 UTRN- 0.66132939 0.00638037 1092UTRN- 10000 HSKM 240 qRTPCR 53 m01 16 238467 UTRN- 0.52348932 0.132551861092 UTRN- 10000 HSKM 240 qRTPCR 54 m01 16 242264 UTRN- 0.436409960.072764 1092 UTRN- 10000 HSKM 240 qRTPCR 55 m01 16 251939 UTRN-0.63988557 0.11520213 1092 UTRN- 10000 HSKM 240 qRTPCR 56 m01 16 453443UTRN- 0.93462493 0.18712741 1092 UTRN- 10000 HSKM 240 qRTPCR 57 m01 16453483 UTRN- 0.75940222 0.0719666 1092 UTRN- 10000 HSKM 240 qRTPCR 58m01 16 456038 UTRN- 0.83102612 0.09768756 1092 UTRN- 10000 HSKM 240qRTPCR 59 m01 16 272301 UTRN- 0.90452397 0.03259764 1092 UTRN- 10000HSKM 240 qRTPCR 60 m01 16 276749 UTRN- 0.43497163 0.04443017 1092 UTRN-10000 HSKM 240 qRTPCR 61 m01 16 289697 UTRN- 0.52034725 0.08101528 1092UTRN- 10000 HSKM 240 qRTPCR 62 m01 16 292490 UTRN- 2.09680006 0.290379711092 UTRN- 10000 HSKM 240 qRTPCR 63 m01 16 292535 UTRN- 0.474565840.04190501 1092 UTRN- 10000 HSKM 240 qRTPCR 64 m01 16 292541 UTRN-0.67792191 0.14377542 1092 UTRN- 10000 HSKM 240 qRTPCR 65 m01 16 Ctrl Un1 0.06312076 1092 UTRN- 10000 HSKM 240 qRTPCR 16 313770 UTRN- 0.75757750.06519882 1093 UTRN- 10 SK-N- 96 qRTPCR 01 m01 16 AS 5776 UTRN-0.85222427 0.10789825 1093 UTRN- 10 SK-N- 96 qRTPCR 02 m01 16 AS 5781UTRN- 1.01396082 0.09810241 1093 UTRN- 10 SK-N- 96 qRTPCR 03 m01 16 AS32192 UTRN- 1.03810301 0.03479278 1093 UTRN- 10 SK-N- 96 qRTPCR 04 m0116 AS 39558 UTRN- 0.83811001 0.07880378 1093 UTRN- 10 SK-N- 96 qRTPCR 05m01 16 AS 45784 UTRN- 0.83497824 0.07648946 1093 UTRN- 10 SK-N- 96qRTPCR 06 m01 16 AS 60002 UTRN- 0.96839775 0.01027857 1093 UTRN- 10SK-N- 96 qRTPCR 07 m01 16 AS 60035 UTRN- 0.75617386 0.07285202 1093UTRN- 10 SK-N- 96 qRTPCR 08 m01 16 AS 60038 UTRN- 0.7312052 0.103689881093 UTRN- 10 SK-N- 96 qRTPCR 09 m01 16 AS 336679 UTRN- 0.791998880.02149166 1093 UTRN- 10 SK-N- 96 qRTPCR 10 m01 16 AS 62709 UTRN-0.83242213 0.06016044 1093 UTRN- 10 SK-N- 96 qRTPCR 11 m01 16 AS 64394UTRN- 0.64519349 0.01424472 1093 UTRN- 10 SK-N- 96 qRTPCR 12 m01 16 AS64407 UTRN- 1.11054003 0.18126866 1093 UTRN- 10 SK-N- 96 qRTPCR 13 m0116 AS 68368 UTRN- 0.88642258 0.02610345 1093 UTRN- 10 SK-N- 96 qRTPCR 14m01 16 AS 68420 UTRN- 0.97809677 0.03996164 1093 UTRN- 10 SK-N- 96qRTPCR 15 m01 16 AS 68424 UTRN- 1.05603303 0.0221464 1093 UTRN- 10 SK-N-96 qRTPCR 16 m01 16 AS 82947 UTRN- 0.86484877 0.03445718 1093 UTRN- 10SK-N- 96 qRTPCR 17 m01 16 AS 85204 UTRN- 0.87523415 0.06143543 1093UTRN- 10 SK-N- 96 qRTPCR 18 m01 16 AS 89541 UTRN- 0.81075428 0.061336221093 UTRN- 10 SK-N- 96 qRTPCR 19 m01 16 AS 355024 UTRN- 0.883112120.09117433 1093 UTRN- 10 SK-N- 96 qRTPCR 20 m01 16 AS 99210 UTRN-0.74490634 0.07508644 1093 UTRN- 10 SK-N- 96 qRTPCR 21 m01 16 AS 101919UTRN- 1.02899798 0.08963731 1093 UTRN- 10 SK-N- 96 qRTPCR 22 m01 16 AS101994 UTRN- 0.68475403 0.07475312 1093 UTRN- 10 SK-N- 96 qRTPCR 23 m0116 AS 103832 UTRN- 1.1636468 0.02059317 1093 UTRN- 10 SK-N- 96 qRTPCR 24m01 16 AS 103833 UTRN- 1.0058327 0.07356244 1093 UTRN- 10 SK-N- 96qRTPCR 25 m01 16 AS 103853 UTRN- 0.91569873 0.04941268 1093 UTRN- 10SK-N- 96 qRTPCR 26 m01 16 AS 103933 UTRN- 1.02643259 0.09834793 1093UTRN- 10 SK-N- 96 qRTPCR 27 m01 16 AS 117420 UTRN- 0.89445462 0.061286671093 UTRN- 10 SK-N- 96 qRTPCR 28 m01 16 AS 120115 UTRN- 1.487618030.15210318 1093 UTRN- 10 SK-N- 96 qRTPCR 29 m01 16 AS 120121 UTRN-0.99624217 0.09012073 1093 UTRN- 10 SK-N- 96 qRTPCR 30 m01 16 AS Ctrl Un1.15935157 0.09751773 1093 UTRN- 10 SK-N- 96 qRTPCR 16 AS Ctrl 10.15131056 1093 UTRN- 10 SK-N- 96 qRTPCR Lipo 16 AS 362061 UTRN-0.89501129 0.10526106 1093 UTRN- 10 SK-N- 96 qRTPCR 31 m01 16 AS 372488UTRN- 0.91931779 0.04115957 1093 UTRN- 10 SK-N- 96 qRTPCR 32 m01 16 AS372542 UTRN- 0.9257933 0.10415883 1093 UTRN- 10 SK-N- 96 qRTPCR 33 m0116 AS 376352 UTRN- 0.91402177 0.11538068 1093 UTRN- 10 SK-N- 96 qRTPCR34 m01 16 AS 139243 UTRN- 0.64416032 0.02961176 1093 UTRN- 10 SK-N- 96qRTPCR 35 m01 16 AS 143189 UTRN- 0.79446545 0.08975342 1093 UTRN- 10SK-N- 96 qRTPCR 36 m01 16 AS 151630 UTRN- 1.08229119 0.15428042 1093UTRN- 10 SK-N- 96 qRTPCR 37 m01 16 AS 166370 UTRN- 0.73170896 0.116840011093 UTRN- 10 SK-N- 96 qRTPCR 38 m01 16 AS 166372 UTRN- 0.837364630.04842828 1093 UTRN- 10 SK-N- 96 qRTPCR 39 m01 16 AS 169368 UTRN-1.00571931 0.09657045 1093 UTRN- 10 SK-N- 96 qRTPCR 40 m01 16 AS 399345UTRN- 0.66794056 0.12852317 1093 UTRN- 10 SK-N- 96 qRTPCR 41 m01 16 AS412519 UTRN- 0.80972813 0.03420812 1093 UTRN- 10 SK-N- 96 qRTPCR 42 m0116 AS 412600 UTRN- 0.93184181 0.0330165 1093 UTRN- 10 SK-N- 96 qRTPCR 43m01 16 AS 414862 UTRN- 0.7780304 0.0640387 1093 UTRN- 10 SK-N- 96 qRTPCR44 m01 16 AS 195707 UTRN- 0.7646356 0.11294998 1093 UTRN- 10 SK-N- 96qRTPCR 45 m01 16 AS 422943 UTRN- 1.03916407 0.18471623 1093 UTRN- 10SK-N- 96 qRTPCR 46 m01 16 AS 422946 UTRN- 0.78047667 0.05266601 1093UTRN- 10 SK-N- 96 qRTPCR 47 m01 16 AS 210674 UTRN- 0.69055555 0.002720251093 UTRN- 10 SK-N- 96 qRTPCR 48 m01 16 AS 426032 UTRN- 0.97315030.09896712 1093 UTRN- 10 SK-N- 96 qRTPCR 49 m01 16 AS 225629 UTRN-0.65724116 0.02090648 1093 UTRN- 10 SK-N- 96 qRTPCR 50 m01 16 AS 225662UTRN- 0.87698771 0.12228726 1093 UTRN- 10 SK-N- 96 qRTPCR 51 m01 16 AS229456 UTRN- 1.08973844 0.09000559 1093 UTRN- 10 SK-N- 96 qRTPCR 52 m0116 AS 436557 UTRN- 0.81611016 0.03686041 1093 UTRN- 10 SK-N- 96 qRTPCR53 m01 16 AS 238467 UTRN- 0.93870312 0.06965803 1093 UTRN- 10 SK-N- 96qRTPCR 54 m01 16 AS 242264 UTRN- 0.82889014 0.17454161 1093 UTRN- 10SK-N- 96 qRTPCR 55 m01 16 AS 251939 UTRN- 1.13435171 0.17819815 1093UTRN- 10 SK-N- 96 qRTPCR 56 m01 16 AS 453443 UTRN- 1.3064641 0.260259141093 UTRN- 10 SK-N- 96 qRTPCR 57 m01 16 AS 453483 UTRN- 0.848106010.11631749 1093 UTRN- 10 SK-N- 96 qRTPCR 58 m01 16 AS 456038 UTRN-0.74549699 0.03267881 1093 UTRN- 10 SK-N- 96 qRTPCR 59 m01 16 AS 272301UTRN- 1.19595592 0.13571268 1093 UTRN- 10 SK-N- 96 qRTPCR 60 m01 16 ASCtrl Un 1.05713903 0.11259158 1093 UTRN- 10 SK-N- 96 qRTPCR 16 AS Ctrl 10.08245938 1093 UTRN- 10 SK-N- 96 qRTPCR Lipo 16 AS 276749 UTRN-1.03127416 0.10921988 1093 UTRN- 10 SK-N- 96 qRTPCR 61 m01 16 AS 289697UTRN- 1.044169 0.03233713 1093 UTRN- 10 SK-N- 96 qRTPCR 62 m01 16 AS292490 UTRN- 1.52465937 0.09572692 1093 UTRN- 10 SK-N- 96 qRTPCR 63 m0116 AS 292535 UTRN- 1.1321036 0.05236107 1093 UTRN- 10 SK-N- 96 qRTPCR 64m01 16 AS 292541 UTRN- 1.08228927 0.13345192 1093 UTRN- 10 SK-N- 96qRTPCR 65 m01 16 AS Ctrl 1 0.05709597 1093 UTRN- 10 SK-N- 96 qRTPCR Lipo16 AS Ctrl Un 1.47130024 0.02213981 1093 UTRN- 10 SK-N- 96 qRTPCR 16 AS313770 UTRN- 0.60984478 0.06309994 1093 UTRN- 30 SK-N- 96 qRTPCR 01 m0116 AS 5776 UTRN- 0.89147593 0.13375976 1093 UTRN- 30 SK-N- 96 qRTPCR 02m01 16 AS 5781 UTRN- 0.61855672 0.02207853 1093 UTRN- 30 SK-N- 96 qRTPCR03 m01 16 AS 32192 UTRN- 1.28418183 0.15451636 1093 UTRN- 30 SK-N- 96qRTPCR 04 m01 16 AS 39558 UTRN- 0.52634941 0.02812606 1093 UTRN- 30SK-N- 96 qRTPCR 05 m01 16 AS 45784 UTRN- 0.71111335 0.08563004 1093UTRN- 30 SK-N- 96 qRTPCR 06 m01 16 AS 60002 UTRN- 0.99729465 0.112351941093 UTRN- 30 SK-N- 96 qRTPCR 07 m01 16 AS 60035 UTRN- 0.863871590.18316087 1093 UTRN- 30 SK-N- 96 qRTPCR 08 m01 16 AS 60038 UTRN-0.72007659 0.24804121 1093 UTRN- 30 SK-N- 96 qRTPCR 09 m01 16 AS 336679UTRN- 0.86416247 0.34064684 1093 UTRN- 30 SK-N- 96 qRTPCR 10 m01 16 AS62709 UTRN- 0.8083888 0.08325476 1093 UTRN- 30 SK-N- 96 qRTPCR 11 m01 16AS 64394 UTRN- 0.66395045 0.0899959 1093 UTRN- 30 SK-N- 96 qRTPCR 12 m0116 AS 64407 UTRN- 1.67089265 0.2291624 1093 UTRN- 30 SK-N- 96 qRTPCR 13m01 16 AS 68368 UTRN- 1.025824 0.22573532 1093 UTRN- 30 SK-N- 96 qRTPCR14 m01 16 AS 68420 UTRN- 0.73754467 0.09940368 1093 UTRN- 30 SK-N- 96qRTPCR 15 m01 16 AS 68424 UTRN- 0.94217145 0.1721728 1093 UTRN- 30 SK-N-96 qRTPCR 16 m01 16 AS 82947 UTRN- 0.58124677 0.04563767 1093 UTRN- 30SK-N- 96 qRTPCR 17 m01 16 AS 85204 UTRN- 0.61668486 0.05784673 1093UTRN- 30 SK-N- 96 qRTPCR 18 m01 16 AS 89541 UTRN- 0.54982484 0.091850931093 UTRN- 30 SK-N- 96 qRTPCR 19 m01 16 AS 355024 UTRN- 0.674558740.19009293 1093 UTRN- 30 SK-N- 96 qRTPCR 20 m01 16 AS 99210 UTRN-0.58343685 0.04620854 1093 UTRN- 30 SK-N- 96 qRTPCR 21 m01 16 AS 101919UTRN- 1.48440599 0.26778843 1093 UTRN- 30 SK-N- 96 qRTPCR 22 m01 16 AS101994 UTRN- 0.81907189 0.0273814 1093 UTRN- 30 SK-N- 96 qRTPCR 23 m0116 AS 103832 UTRN- 1.25868392 0.17591054 1093 UTRN- 30 SK-N- 96 qRTPCR24 m01 16 AS 103833 UTRN- 1.0311567 0.11744487 1093 UTRN- 30 SK-N- 96qRTPCR 25 m01 16 AS 103853 UTRN- 0.72249989 0.11346444 1093 UTRN- 30SK-N- 96 qRTPCR 26 m01 16 AS 103933 UTRN- 1.18559662 0.06292947 1093UTRN- 30 SK-N- 96 qRTPCR 27 m01 16 AS 117420 UTRN- 1.61312748 0.024768361093 UTRN- 30 SK-N- 96 qRTPCR 28 m01 16 AS 120115 UTRN- 1.00510880.15356527 1093 UTRN- 30 SK-N- 96 qRTPCR 29 m01 16 AS 120121 UTRN-0.92694391 0.13136339 1093 UTRN- 30 SK-N- 96 qRTPCR 30 m01 16 AS Ctrl Un1.05582073 0.16466874 1093 UTRN- 30 SK-N- 96 qRTPCR 16 AS Ctrl 10.101077 1093 UTRN- 30 SK-N- 96 qRTPCR Lipo 16 AS 362061 UTRN-0.50511184 0.01784854 1093 UTRN- 30 SK-N- 96 qRTPCR 31 m01 16 AS 372488UTRN- 0.80809669 0.00211969 1093 UTRN- 30 SK-N- 96 qRTPCR 32 m01 16 AS372542 UTRN- 0.65771104 0.06565461 1093 UTRN- 30 SK-N- 96 qRTPCR 33 m0116 AS 376352 UTRN- 0.5431115 0.02628406 1093 UTRN- 30 SK-N- 96 qRTPCR 34m01 16 AS 139243 UTRN- 0.56264098 0.05675936 1093 UTRN- 30 SK-N- 96qRTPCR 35 m01 16 AS 143189 UTRN- 0.57779435 0.02631325 1093 UTRN- 30SK-N- 96 qRTPCR 36 m01 16 AS 151630 UTRN- 0.50337944 0.05884767 1093UTRN- 30 SK-N- 96 qRTPCR 37 m01 16 AS 166370 UTRN- 0.32025952 0.012867911093 UTRN- 30 SK-N- 96 qRTPCR 38 m01 16 AS 166372 UTRN- 0.607145230.02373014 1093 UTRN- 30 SK-N- 96 qRTPCR 39 m01 16 AS 169368 UTRN-1.12335489 0.19727474 1093 UTRN- 30 SK-N- 96 qRTPCR 40 m01 16 AS 399345UTRN- 0.49256976 0.04675795 1093 UTRN- 30 SK-N- 96 qRTPCR 41 m01 16 AS412519 UTRN- 0.68909557 0.03904239 1093 UTRN- 30 SK-N- 96 qRTPCR 42 m0116 AS 412600 UTRN- 0.96488878 0.20588734 1093 UTRN- 30 SK-N- 96 qRTPCR43 m01 16 AS 414862 UTRN- 0.52495952 0.08382155 1093 UTRN- 30 SK-N- 96qRTPCR 44 m01 16 AS 195707 UTRN- 0.73795336 0.05541599 1093 UTRN- 30SK-N- 96 qRTPCR 45 m01 16 AS 422943 UTRN- 0.74085667 0.06637287 1093UTRN- 30 SK-N- 96 qRTPCR 46 m01 16 AS 422946 UTRN- 0.42761568 0.017729151093 UTRN- 30 SK-N- 96 qRTPCR 47 m01 16 AS 210674 UTRN- 0.587807870.02910385 1093 UTRN- 30 SK-N- 96 qRTPCR 48 m01 16 AS 426032 UTRN-0.7296564 0.02867856 1093 UTRN- 30 SK-N- 96 qRTPCR 49 m01 16 AS 225629UTRN- 0.40395121 0.03201391 1093 UTRN- 30 SK-N- 96 qRTPCR 50 m01 16 AS225662 UTRN- 0.83099737 0.12029916 1093 UTRN- 30 SK-N- 96 qRTPCR 51 m0116 AS 229456 UTRN- 0.77073083 0.16512396 1093 UTRN- 30 SK-N- 96 qRTPCR52 m01 16 AS 436557 UTRN- 0.48278404 0.01573001 1093 UTRN- 30 SK-N- 96qRTPCR 53 m01 16 AS 238467 UTRN- 0.49363203 0.08427735 1093 UTRN- 30SK-N- 96 qRTPCR 54 m01 16 AS 242264 UTRN- 0.69749568 0.03277514 1093UTRN- 30 SK-N- 96 qRTPCR 55 m01 16 AS 251939 UTRN- 0.59481116 0.074762381093 UTRN- 30 SK-N- 96 qRTPCR 56 m01 16 AS 453443 UTRN- 1.082752040.0676891 1093 UTRN- 30 SK-N- 96 qRTPCR 57 m01 16 AS 453483 UTRN-0.37405908 0.03151226 1093 UTRN- 30 SK-N- 96 qRTPCR 58 m01 16 AS 456038UTRN- 0.34267879 0.04428324 1093 UTRN- 30 SK-N- 96 qRTPCR 59 m01 16 AS272301 UTRN- 0.77142847 0.04819709 1093 UTRN- 30 SK-N- 96 qRTPCR 60 m0116 AS Ctrl Un 0.77092848 0.16407024 1093 UTRN- 30 SK-N- 96 qRTPCR 16 ASCtrl 1 0.1342955 1093 UTRN- 30 SK-N- 96 qRTPCR Lipo 16 AS 276749 UTRN-0.65483288 0.07342203 1093 UTRN- 30 SK-N- 96 qRTPCR 61 m01 16 AS 289697UTRN- 0.98337602 0.13676097 1093 UTRN- 30 SK-N- 96 qRTPCR 62 m01 16 AS292490 UTRN- 2.58061127 0.15400488 1093 UTRN- 30 SK-N- 96 qRTPCR 63 m0116 AS 292535 UTRN- 0.88372096 0.03014721 1093 UTRN- 30 SK-N- 96 qRTPCR64 m01 16 AS 292541 UTRN- 0.9736869 0.04890107 1093 UTRN- 30 SK-N- 96qRTPCR 65 m01 16 AS Ctrl 1 0.08104028 1093 UTRN- 30 SK-N- 96 qRTPCR Lipo16 AS Ctrl Un 1.20258604 0.15138558 1093 UTRN- 30 SK-N- 96 qRTPCR 16 AS313770 UTRN- 0.32616792 0.02185726 1094 UTRN- 50 am002fDMD 96 qRTPCR 01m01 16 5776 UTRN- 1.01669863 0.0462533 1094 UTRN- 50 am002fDMD 96 qRTPCR02 m01 16 5781 UTRN- 0.70233657 0.0250169 1094 UTRN- 50 am002fDMD 96qRTPCR 03 m01 16 32192 UTRN- 1.59956172 0.13696613 1094 UTRN- 50am002fDMD 96 qRTPCR 04 m01 16 39558 UTRN- 0.58957401 0.02802524 1094UTRN- 50 am002fDMD 96 qRTPCR 05 m01 16 45784 UTRN- 1.0334611 0.007775421094 UTRN- 50 am002fDMD 96 qRTPCR 06 m01 16 60002 UTRN- 0.761430580.02768371 1094 UTRN- 50 am002fDMD 96 qRTPCR 07 m01 16 60035 UTRN-0.39512861 0.00936128 1094 UTRN- 50 am002fDMD 96 qRTPCR 08 m01 16 60038UTRN- 0.34012174 0.01623502 1094 UTRN- 50 am002fDMD 96 qRTPCR 09 m01 16336679 UTRN- 0.38868099 0.01886348 1094 UTRN- 50 am002fDMD 96 qRTPCR 10m01 16 62709 UTRN- 0.50986245 0.03047854 1094 UTRN- 50 am002fDMD 96qRTPCR 11 m01 16 64394 UTRN- 0.60028491 0.00721445 1094 UTRN- 50am002fDMD 96 qRTPCR 12 m01 16 64407 UTRN- 0.72114801 0.0075241 1094UTRN- 50 am002fDMD 96 qRTPCR 13 m01 16 68368 UTRN- 1.12622763 0.033674781094 UTRN- 50 am002fDMD 96 qRTPCR 14 m01 16 68420 UTRN- 0.538914520.01936459 1094 UTRN- 50 am002fDMD 96 qRTPCR 15 m01 16 68424 UTRN-1.11183444 0.04790854 1094 UTRN- 50 am002fDMD 96 qRTPCR 16 m01 16 82947UTRN- 0.82497461 0.03386966 1094 UTRN- 50 am002fDMD 96 qRTPCR 17 m01 1685204 UTRN- 0.79359523 0.03608986 1094 UTRN- 50 am002fDMD 96 qRTPCR 18m01 16 89541 UTRN- 0.28545383 0.01787595 1094 UTRN- 50 am002fDMD 96qRTPCR 19 m01 16 355024 UTRN- 0.92181838 0.08353234 1094 UTRN- 50am002fDMD 96 qRTPCR 20 m01 16 99210 UTRN- 0.64207739 0.02593464 1094UTRN- 50 am002fDMD 96 qRTPCR 21 m01 16 101919 UTRN- 1.372668090.03108759 1094 UTRN- 50 am002fDMD 96 qRTPCR 22 m01 16 101994 UTRN-0.58216388 0.02158436 1094 UTRN- 50 am002fDMD 96 qRTPCR 23 m01 16 103832UTRN- 1.45704637 0.04091926 1094 UTRN- 50 am002fDMD 96 qRTPCR 24 m01 16276749 UTRN- 0.62942509 0.01705386 1094 UTRN- 50 am002fDMD 96 qRTPCR 61m01 16 289697 UTRN- 1.01437442 0.08211814 1094 UTRN- 50 am002fDMD 96qRTPCR 62 m01 16 292490 UTRN- 1.4085666 0.13479916 1094 UTRN- 50am002fDMD 96 qRTPCR 63 m01 16 292535 UTRN- 0.58443353 0.02574256 1094UTRN- 50 am002fDMD 96 qRTPCR 64 m01 16 292541 UTRN- 0.44749637 0.0196561094 UTRN- 50 am002fDMD 96 qRTPCR 65 m01 16 Ctrl Un 1.29398342 0.0106211094 UTRN- 50 am002fDMD 96 qRTPCR 16 Ctrl 1 0.0266363 1094 UTRN- 50am002fDMD 96 qRTPCR Lipo 16 313770 UTRN- 0.20006344 0.04798471 1094UTRN- 50 am002fDMD 96 qRTPCR 01 m01 69 5776 UTRN- 0.37542754 0.068570961094 UTRN- 50 am002fDMD 96 qRTPCR 02 m01 69 5781 UTRN- 0.318321930.05945466 1094 UTRN- 50 am002fDMD 96 qRTPCR 03 m01 69 32192 UTRN-1.03183123 0.08239389 1094 UTRN- 50 am002fDMD 96 qRTPCR 04 m01 69 39558UTRN- 0.9687712 0.03993136 1094 UTRN- 50 am002fDMD 96 qRTPCR 05 m01 6945784 UTRN- 0.8351518 0.0399697 1094 UTRN- 50 am002fDMD 96 qRTPCR 06 m0169 60002 UTRN- 0.4479661 0.02933481 1094 UTRN- 50 am002fDMD 96 qRTPCR 07m01 69 60035 UTRN- 0.52003364 0.01872176 1094 UTRN- 50 am002fDMD 96qRTPCR 08 m01 69 60038 UTRN- 0.32456103 0.01192516 1094 UTRN- 50am002fDMD 96 qRTPCR 09 m01 69 336679 UTRN- 0.58129219 0.02357231 1094UTRN- 50 am002fDMD 96 qRTPCR 10 m01 69 62709 UTRN- 0.49243556 0.020665441094 UTRN- 50 am002fDMD 96 qRTPCR 11 m01 69 64394 UTRN- 0.631436650.03874973 1094 UTRN- 50 am002fDMD 96 qRTPCR 12 m01 69 64407 UTRN-1.14355459 0.05682408 1094 UTRN- 50 am002fDMD 96 qRTPCR 13 m01 69 68368UTRN- 0.42045044 0.05763665 1094 UTRN- 50 am002fDMD 96 qRTPCR 14 m01 6968420 UTRN- 0.68441644 0.05478663 1094 UTRN- 50 am002fDMD 96 qRTPCR 15m01 69 68424 UTRN- 0.58821005 0.04014146 1094 UTRN- 50 am002fDMD 96qRTPCR 16 m01 69 82947 UTRN- 0.36863122 0.03598423 1094 UTRN- 50am002fDMD 96 qRTPCR 17 m01 69 85204 UTRN- 0.66171976 0.0178607 1094UTRN- 50 am002fDMD 96 qRTPCR 18 m01 69 89541 UTRN- 0.11822583 0.014937431094 UTRN- 50 am002fDMD 96 qRTPCR 19 m01 69 355024 UTRN- 0.700824830.07992993 1094 UTRN- 50 am002fDMD 96 qRTPCR 20 m01 69 99210 UTRN-0.71340219 0.05198843 1094 UTRN- 50 am002fDMD 96 qRTPCR 21 m01 69 101919UTRN- 0.45449951 0.04236762 1094 UTRN- 50 am002fDMD 96 qRTPCR 22 m01 69101994 UTRN- 0.63994873 0.02817303 1094 UTRN- 50 am002fDMD 96 qRTPCR 23m01 69 103832 UTRN- 0.88092337 0.05871034 1094 UTRN- 50 am002fDMD 96qRTPCR 24 m01 69 276749 UTRN- 0.23006675 0.03780199 1094 UTRN- 50am002fDMD 96 qRTPCR 61 m01 69 289697 UTRN- 1.12844673 0.17967005 1094UTRN- 50 am002fDMD 96 qRTPCR 62 m01 69 292490 UTRN- 0.184333230.03485563 1094 UTRN- 50 am002fDMD 96 qRTPCR 63 m01 69 292535 UTRN-0.17433798 0.01365184 1094 UTRN- 50 am002fDMD 96 qRTPCR 64 m01 69 292541UTRN- 0.50196292 0.0491373 1094 UTRN- 50 am002fDMD 96 qRTPCR 65 m01 69Ctrl Un 2.13645092 0.09730565 1094 UTRN- 50 am002fDMD 96 qRTPCR 69 Ctrl1 0.10157931 1094 UTRN- 50 am002fDMD 96 qRTPCR Lipo 69 313770 UTRN-0.27016057 0.0537116 1094 UTRN- 50 am002fDMD 96 qRTPCR 01 m01 02 5776UTRN- 0.43755894 0.05761395 1094 UTRN- 50 am002fDMD 96 qRTPCR 02 m01 025781 UTRN- 0.41249459 0.02943631 1094 UTRN- 50 am002fDMD 96 qRTPCR 03m01 02 32192 UTRN- 1.11519083 0.07430174 1094 UTRN- 50 am002fDMD 96qRTPCR 04 m01 02 39558 UTRN- 1.01159292 0.0262187 1094 UTRN- 50am002fDMD 96 qRTPCR 05 m01 02 45784 UTRN- 0.89969233 0.01062374 1094UTRN- 50 am002fDMD 96 qRTPCR 06 m01 02 60002 UTRN- 0.55175558 0.048810931094 UTRN- 50 am002fDMD 96 qRTPCR 07 m01 02 60035 UTRN- 0.58225590.03667059 1094 UTRN- 50 am002fDMD 96 qRTPCR 08 m01 02 60038 UTRN-0.35245532 0.04133 1094 UTRN- 50 am002fDMD 96 qRTPCR 09 m01 02 336679UTRN- 0.55047495 0.02207268 1094 UTRN- 50 am002fDMD 96 qRTPCR 10 m01 0262709 UTRN- 0.41783956 0.0209482 1094 UTRN- 50 am002fDMD 96 qRTPCR 11m01 02 64394 UTRN- 0.53338875 0.0270747 1094 UTRN- 50 am002fDMD 96qRTPCR 12 m01 02 64407 UTRN- 1.17230576 0.08108839 1094 UTRN- 50am002fDMD 96 qRTPCR 13 m01 02 68368 UTRN- 0.54787389 0.09693453 1094UTRN- 50 am002fDMD 96 qRTPCR 14 m01 02 68420 UTRN- 0.71271868 0.067548011094 UTRN- 50 am002fDMD 96 qRTPCR 15 m01 02 68424 UTRN- 0.295795550.02408746 1094 UTRN- 50 am002fDMD 96 qRTPCR 16 m01 02 82947 UTRN-0.36760298 0.03225722 1094 UTRN- 50 am002fDMD 96 qRTPCR 17 m01 02 85204UTRN- 0.71687906 0.02515345 1094 UTRN- 50 am002fDMD 96 qRTPCR 18 m01 0289541 UTRN- 0.1380875 0.01926532 1094 UTRN- 50 am002fDMD 96 qRTPCR 19m01 02 355024 UTRN- 0.7078851 0.04532949 1094 UTRN- 50 am002fDMD 96qRTPCR 20 m01 02 99210 UTRN- 0.68991983 0.03857872 1094 UTRN- 50am002fDMD 96 qRTPCR 21 m01 02 101919 UTRN- 0.49654219 0.05756049 1094UTRN- 50 am002fDMD 96 qRTPCR 22 m01 02 101994 UTRN- 0.641666640.03200979 1094 UTRN- 50 am002fDMD 96 qRTPCR 23 m01 02 103832 UTRN-0.86083828 0.08223742 1094 UTRN- 50 am002fDMD 96 qRTPCR 24 m01 02 276749UTRN- 0.36924754 0.03271067 1094 UTRN- 50 am002fDMD 96 qRTPCR 61 m01 02289697 UTRN- 1.30122081 0.21051853 1094 UTRN- 50 am002fDMD 96 qRTPCR 62m01 02 292490 UTRN- 0.24329494 0.01817197 1094 UTRN- 50 am002fDMD 96qRTPCR 63 m01 02 292535 UTRN- 0.17744299 0.01532655 1094 UTRN- 50am002fDMD 96 qRTPCR 64 m01 02 292541 UTRN- 0.55237323 0.01848998 1094UTRN- 50 am002fDMD 96 qRTPCR 65 m01 02 Ctrl Un 2.36606122 0.101162891094 UTRN- 50 am002fDMD 96 qRTPCR 02 Ctrl 1 0.07587432 1094 UTRN- 50am002fDMD 96 qRTPCR Lipo 02 313770 UTRN- 0.23166392 0.03986326 1095UTRN- 50 am002fDMD 168 qRTPCR 01 m01 16 5776 UTRN- 0.7562623 0.032181521095 UTRN- 50 am002fDMD 168 qRTPCR 02 m01 16 5781 UTRN- 0.682061960.07354295 1095 UTRN- 50 am002fDMD 168 qRTPCR 03 m01 16 32192 UTRN-1.38957133 0.07032511 1095 UTRN- 50 am002fDMD 168 qRTPCR 04 m01 16 39558UTRN- 0.77569544 0.02262853 1095 UTRN- 50 am002fDMD 168 qRTPCR 05 m01 1645784 UTRN- 1.43617331 0.02530774 1095 UTRN- 50 am002fDMD 168 qRTPCR 06m01 16 60002 UTRN- 0.99220334 0.07921071 1095 UTRN- 50 am002fDMD 168qRTPCR 07 m01 16 60035 UTRN- 0.46517717 0.03573208 1095 UTRN- 50am002fDMD 168 qRTPCR 08 m01 16 60038 UTRN- 0.46125504 0.00935883 1095UTRN- 50 am002fDMD 168 qRTPCR 09 m01 16 336679 UTRN- 0.687541210.02920918 1095 UTRN- 50 am002fDMD 168 qRTPCR 10 m01 16 62709 UTRN-0.60949652 0.06010728 1095 UTRN- 50 am002fDMD 168 qRTPCR 11 m01 16 64394UTRN- 0.44118491 0.01910906 1095 UTRN- 50 am002fDMD 168 qRTPCR 12 m01 1664407 UTRN- 1.03529403 0.07129539 1095 UTRN- 50 am002fDMD 168 qRTPCR 13m01 16 68368 UTRN- 0.99785237 0.00277169 1095 UTRN- 50 am002fDMD 168qRTPCR 14 m01 16 68420 UTRN- 0.58229001 0.03433043 1095 UTRN- 50am002fDMD 168 qRTPCR 15 m01 16 68424 UTRN- 1.07785244 0.05088514 1095UTRN- 50 am002fDMD 168 qRTPCR 16 m01 16 82947 UTRN- 1.133088490.08727186 1095 UTRN- 50 am002fDMD 168 qRTPCR 17 m01 16 85204 UTRN-0.88827948 0.02553011 1095 UTRN- 50 am002fDMD 168 qRTPCR 18 m01 16 89541UTRN- 0.43785575 0.03625092 1095 UTRN- 50 am002fDMD 168 qRTPCR 19 m01 16355024 UTRN- 1.03615197 0.10728058 1095 UTRN- 50 am002fDMD 168 qRTPCR 20m01 16 99210 UTRN- 0.8493589 0.02109217 1095 UTRN- 50 am002fDMD 168qRTPCR 21 m01 16 101919 UTRN- 1.13406358 0.07848721 1095 UTRN- 50am002fDMD 168 qRTPCR 22 m01 16 101994 UTRN- 0.78537651 0.03787308 1095UTRN- 50 am002fDMD 168 qRTPCR 23 m01 16 103832 UTRN- 1.579593870.02118097 1095 UTRN- 50 am002fDMD 168 qRTPCR 24 m01 16 276749 UTRN-0.27696413 0.0278247 1095 UTRN- 50 am002fDMD 168 qRTPCR 61 m01 16 289697UTRN- 1.02583443 0.09132877 1095 UTRN- 50 am002fDMD 168 qRTPCR 62 m01 16292490 UTRN- 1.36321054 0.02279074 1095 UTRN- 50 am002fDMD 168 qRTPCR 63m01 16 292535 UTRN- 0.80272169 0.03558919 1095 UTRN- 50 am002fDMD 168qRTPCR 64 m01 16 292541 UTRN- 0.45138121 0.03952107 1095 UTRN- 50am002fDMD 168 qRTPCR 65 m01 16 Ctrl Un 1.05925262 0.05760247 1095 UTRN-50 am002fDMD 168 qRTPCR 16 Ctrl 1 0.03057386 1095 UTRN- 50 am002fDMD 168qRTPCR Lipo 16 313770 UTRN- 0.75055397 0.05191791 1096 UTRN- 30am002fDMD 240 qRTPCR 01 m01 16 5776 UTRN- 0.93267894 0.08361127 1096UTRN- 30 am002fDMD 240 qRTPCR 02 m01 16 5781 UTRN- 0.8459375 0.068984791096 UTRN- 30 am002fDMD 240 qRTPCR 03 m01 16 32192 UTRN- 0.948068810.00727076 1096 UTRN- 30 am002fDMD 240 qRTPCR 04 m01 16 39558 UTRN-0.85548543 0.02685995 1096 UTRN- 30 am002fDMD 240 qRTPCR 05 m01 16 45784UTRN- 0.87672297 0.08588369 1096 UTRN- 30 am002fDMD 240 qRTPCR 06 m01 1660002 UTRN- 0.91923287 0.03761358 1096 UTRN- 30 am002fDMD 240 qRTPCR 07m01 16 60035 UTRN- 0.85268562 0.01765621 1096 UTRN- 30 am002fDMD 240qRTPCR 08 m01 16 60038 UTRN- 0.75596914 0.03631143 1096 UTRN- 30am002fDMD 240 qRTPCR 09 m01 16 336679 UTRN- 0.84641568 0.10152635 1096UTRN- 30 am002fDMD 240 qRTPCR 10 m01 16 62709 UTRN- 0.69695309 0.0307871096 UTRN- 30 am002fDMD 240 qRTPCR 11 m01 16 64394 UTRN- 0.763276960.0411056 1096 UTRN- 30 am002fDMD 240 qRTPCR 12 m01 16 64407 UTRN-0.82172428 0.0442925 1096 UTRN- 30 am002fDMD 240 qRTPCR 13 m01 16 68368UTRN- 0.76537362 0.01850598 1096 UTRN- 30 am002fDMD 240 qRTPCR 14 m01 1668420 UTRN- 0.78252229 0.02222461 1096 UTRN- 30 am002fDMD 240 qRTPCR 15m01 16 68424 UTRN- 0.90037016 0.04575544 1096 UTRN- 30 am002fDMD 240qRTPCR 16 m01 16 82947 UTRN- 0.95908459 0.07317095 1096 UTRN- 30am002fDMD 240 qRTPCR 17 m01 16 85204 UTRN- 0.80600073 0.05689405 1096UTRN- 30 am002fDMD 240 qRTPCR 18 m01 16 89541 UTRN- 0.690837380.03483852 1096 UTRN- 30 am002fDMD 240 qRTPCR 19 m01 16 355024 UTRN-0.82797369 0.07320327 1096 UTRN- 30 am002fDMD 240 qRTPCR 20 m01 16 99210UTRN- 0.92794361 0.02909557 1096 UTRN- 30 am002fDMD 240 qRTPCR 21 m01 16101919 UTRN- 0.79995775 0.06472403 1096 UTRN- 30 am002fDMD 240 qRTPCR 22m01 16 101994 UTRN- 0.8039519 0.07619583 1096 UTRN- 30 am002fDMD 240qRTPCR 23 m01 16 103832 UTRN- 0.83508016 0.02626351 1096 UTRN- 30am002fDMD 240 qRTPCR 24 m01 16 103833 UTRN- 0.94466345 0.07750392 1096UTRN- 30 am002fDMD 240 qRTPCR 25 m01 16 103853 UTRN- 0.807983640.03361172 1096 UTRN- 30 am002fDMD 240 qRTPCR 26 m01 16 103933 UTRN-0.87984023 0.02147001 1096 UTRN- 30 am002fDMD 240 qRTPCR 27 m01 16117420 UTRN- 0.7320572 0.07556 1096 UTRN- 30 am002fDMD 240 qRTPCR 28 m0116 120115 UTRN- 1.13134523 0.02265497 1096 UTRN- 30 am002fDMD 240 qRTPCR29 m01 16 120121 UTRN- 0.79490416 0.06953964 1096 UTRN- 30 am002fDMD 240qRTPCR 30 m01 16 Ctrl Un 0.84394069 0.04916997 1096 UTRN- 30 am002fDMD240 qRTPCR 16 Ctrl 1 0.06926976 1096 UTRN- 30 am002fDMD 240 qRTPCR Lipo16 362061 UTRN- 0.9709284 0.01153552 1096 UTRN- 30 am002fDMD 240 qRTPCR31 m01 16 372488 UTRN- 1.06867182 0.02106709 1096 UTRN- 30 am002fDMD 240qRTPCR 32 m01 16 372542 UTRN- 1.082223 0.02532558 1096 UTRN- 30am002fDMD 240 qRTPCR 33 m01 16 376352 UTRN- 1.00992377 0.06565572 1096UTRN- 30 am002fDMD 240 qRTPCR 34 m01 16 139243 UTRN- 1.004001910.13229164 1096 UTRN- 30 am002fDMD 240 qRTPCR 35 m01 16 143189 UTRN-1.15434692 0.08027218 1096 UTRN- 30 am002fDMD 240 qRTPCR 36 m01 16151630 UTRN- 0.97730844 0.05076649 1096 UTRN- 30 am002fDMD 240 qRTPCR 37m01 16 166370 UTRN- 1.12892012 0.07118998 1096 UTRN- 30 am002fDMD 240qRTPCR 38 m01 16 166372 UTRN- 1.10114938 0.07594277 1096 UTRN- 30am002fDMD 240 qRTPCR 39 m01 16 169368 UTRN- 1.21178408 0.08044384 1096UTRN- 30 am002fDMD 240 qRTPCR 40 m01 16 399345 UTRN- 1.04171290.03344421 1096 UTRN- 30 am002fDMD 240 qRTPCR 41 m01 16 412519 UTRN-1.07744408 0.06857424 1096 UTRN- 30 am002fDMD 240 qRTPCR 42 m01 16412600 UTRN- 0.92457866 0.03195885 1096 UTRN- 30 am002fDMD 240 qRTPCR 43m01 16 414862 UTRN- 1.05544115 0.03008245 1096 UTRN- 30 am002fDMD 240qRTPCR 44 m01 16 195707 UTRN- 0.98052664 0.09092849 1096 UTRN- 30am002fDMD 240 qRTPCR 45 m01 16 422943 UTRN- 1.09892513 0.01984604 1096UTRN- 30 am002fDMD 240 qRTPCR 46 m01 16 422946 UTRN- 0.794970430.02489728 1096 UTRN- 30 am002fDMD 240 qRTPCR 47 m01 16 210674 UTRN-0.88919709 0.0168988 1096 UTRN- 30 am002fDMD 240 qRTPCR 48 m01 16 426032UTRN- 0.93048326 0.03028883 1096 UTRN- 30 am002fDMD 240 qRTPCR 49 m01 16225629 UTRN- 0.99740207 0.0540456 1096 UTRN- 30 am002fDMD 240 qRTPCR 50m01 16 225662 UTRN- 1.01445304 0.06092202 1096 UTRN- 30 am002fDMD 240qRTPCR 51 m01 16 229456 UTRN- 1.07829975 0.09602393 1096 UTRN- 30am002fDMD 240 qRTPCR 52 m01 16 436557 UTRN- 0.92243319 0.04950107 1096UTRN- 30 am002fDMD 240 qRTPCR 53 m01 16 238467 UTRN- 1.044947040.08420687 1096 UTRN- 30 am002fDMD 240 qRTPCR 54 m01 16 242264 UTRN-0.96138208 0.0238776 1096 UTRN- 30 am002fDMD 240 qRTPCR 55 m01 16 251939UTRN- 0.91868951 0.02782373 1096 UTRN- 30 am002fDMD 240 qRTPCR 56 m01 16453443 UTRN- 0.87955284 0.04179347 1096 UTRN- 30 am002fDMD 240 qRTPCR 57m01 16 453483 UTRN- 0.9414369 0.05421194 1096 UTRN- 30 am002fDMD 240qRTPCR 58 m01 16 456038 UTRN- 0.97625584 0.05408032 1096 UTRN- 30am002fDMD 240 qRTPCR 59 m01 16 272301 UTRN- 1.23338031 0.11033036 1096UTRN- 30 am002fDMD 240 qRTPCR 60 m01 16 Ctrl Un 0.96551729 0.047476531096 UTRN- 30 am002fDMD 240 qRTPCR 16 Ctrl 1 0.0303013 1096 UTRN- 30am002fDMD 240 qRTPCR Lipo 16 276749 UTRN- 0.96970978 0.01935113 1096UTRN- 30 am002fDMD 240 qRTPCR 61 m01 16 289697 UTRN- 1.102600170.06256634 1096 UTRN- 30 am002fDMD 240 qRTPCR 62 m01 16 292490 UTRN-1.22965464 0.08170049 1096 UTRN- 30 am002fDMD 240 qRTPCR 63 m01 16292535 UTRN- 1.14528961 0.02605831 1096 UTRN- 30 am002fDMD 240 qRTPCR 64m01 16 292541 UTRN- 1.12304054 0.0494786 1096 UTRN- 30 am002fDMD 240qRTPCR 65 m01 16 Ctrl 1 0.0328001 1096 UTRN- 30 am002fDMD 240 qRTPCRLipo 16 Ctrl Un 1.06036423 0.07916255 1096 UTRN- 30 am002fDMD 240 qRTPCR16 313770 UTRN- 0.67462825 0.08165038 1097 UTRN- 30 am002fDMD 144 qRTPCR01 m01 16 5776 UTRN- 1.0040793 0.03792203 1097 UTRN- 30 am002fDMD 144qRTPCR 02 m01 16 5781 UTRN- 1.05073108 0.06995556 1097 UTRN- 30am002fDMD 144 qRTPCR 03 m01 16 32192 UTRN- 1.21889789 0.04939547 1097UTRN- 30 am002fDMD 144 qRTPCR 04 m01 16 39558 UTRN- 0.972047260.02800328 1097 UTRN- 30 am002fDMD 144 qRTPCR 05 m01 16 45784 UTRN-1.19749167 0.11502609 1097 UTRN- 30 am002fDMD 144 qRTPCR 06 m01 16 60002UTRN- 1.05892638 0.03195538 1097 UTRN- 30 am002fDMD 144 qRTPCR 07 m01 1660035 UTRN- 0.96059417 0.13090996 1097 UTRN- 30 am002fDMD 144 qRTPCR 08m01 16 60038 UTRN- 0.79396118 0.02398773 1097 UTRN- 30 am002fDMD 144qRTPCR 09 m01 16 336679 UTRN- 1.1137313 0.08926529 1097 UTRN- 30am002fDMD 144 qRTPCR 10 m01 16 62709 UTRN- 1.03710375 0.02946032 1097UTRN- 30 am002fDMD 144 qRTPCR 11 m01 16 64394 UTRN- 1.077337120.03880175 1097 UTRN- 30 am002fDMD 144 qRTPCR 12 m01 16 64407 UTRN-1.11772016 0.04658961 1097 UTRN- 30 am002fDMD 144 qRTPCR 13 m01 16 68368UTRN- 1.07447243 0.06712376 1097 UTRN- 30 am002fDMD 144 qRTPCR 14 m01 1668420 UTRN- 1.10416183 0.01446185 1097 UTRN- 30 am002fDMD 144 qRTPCR 15m01 16 68424 UTRN- 1.22784073 0.01283689 1097 UTRN- 30 am002fDMD 144qRTPCR 16 m01 16 82947 UTRN- 1.13231879 0.02632991 1097 UTRN- 30am002fDMD 144 qRTPCR 17 m01 16 85204 UTRN- 1.18971985 0.07744601 1097UTRN- 30 am002fDMD 144 qRTPCR 18 m01 16 89541 UTRN- 1.064687450.04841277 1097 UTRN- 30 am002fDMD 144 qRTPCR 19 m01 16 355024 UTRN-1.28469255 0.08438321 1097 UTRN- 30 am002fDMD 144 qRTPCR 20 m01 16 99210UTRN- 1.2761479 0.02407821 1097 UTRN- 30 am002fDMD 144 qRTPCR 21 m01 16101919 UTRN- 1.34357124 0.03731536 1097 UTRN- 30 am002fDMD 144 qRTPCR 22m01 16 101994 UTRN- 0.95200968 0.03605078 1097 UTRN- 30 am002fDMD 144qRTPCR 23 m01 16 103832 UTRN- 1.22036161 0.01059834 1097 UTRN- 30am002fDMD 144 qRTPCR 24 m01 16 103833 UTRN- 1.26356309 0.09774877 1097UTRN- 30 am002fDMD 144 qRTPCR 25 m01 16 103853 UTRN- 1.088086160.04569736 1097 UTRN- 30 am002fDMD 144 qRTPCR 26 m01 16 103933 UTRN-1.03276149 0.04356174 1097 UTRN- 30 am002fDMD 144 qRTPCR 27 m01 16117420 UTRN- 1.24524138 0.01823423 1097 UTRN- 30 am002fDMD 144 qRTPCR 28m01 16 120115 UTRN- 1.39018159 0.02601533 1097 UTRN- 30 am002fDMD 144qRTPCR 29 m01 16 120121 UTRN- 1.08224781 0.03837067 1097 UTRN- 30am002fDMD 144 qRTPCR 30 m01 16 Ctrl Un 1.03242662 0.04553206 1097 UTRN-30 am002fDMD 144 qRTPCR 16 Ctrl 1 0.04378138 1097 UTRN- 30 am002fDMD 144qRTPCR Lipo 16 362061 UTRN- 0.76844471 0.02706795 1097 UTRN- 30am002fDMD 144 qRTPCR 31 m01 16 372488 UTRN- 1.08294629 0.02698451 1097UTRN- 30 am002fDMD 144 qRTPCR 32 m01 16 372542 UTRN- 1.410256240.02528352 1097 UTRN- 30 am002fDMD 144 qRTPCR 33 m01 16 376352 UTRN-1.16630314 0.0576001 1097 UTRN- 30 am002fDMD 144 qRTPCR 34 m01 16 139243UTRN- 0.91507564 0.03123946 1097 UTRN- 30 am002fDMD 144 qRTPCR 35 m01 16143189 UTRN- 0.97742097 0.00384429 1097 UTRN- 30 am002fDMD 144 qRTPCR 36m01 16 151630 UTRN- 1.13551038 0.02995458 1097 UTRN- 30 am002fDMD 144qRTPCR 37 m01 16 166370 UTRN- 0.95864002 0.07166238 1097 UTRN- 30am002fDMD 144 qRTPCR 38 m01 16 166372 UTRN- 1.0509856 0.01855711 1097UTRN- 30 am002fDMD 144 qRTPCR 39 m01 16 169368 UTRN- 1.122066780.02649287 1097 UTRN- 30 am002fDMD 144 qRTPCR 40 m01 16 399345 UTRN-1.11991272 0.04296588 1097 UTRN- 30 am002fDMD 144 qRTPCR 41 m01 16412519 UTRN- 1.0642452 0.06414741 1097 UTRN- 30 am002fDMD 144 qRTPCR 42m01 16 412600 UTRN- 1.09166311 0.03507153 1097 UTRN- 30 am002fDMD 144qRTPCR 43 m01 16 414862 UTRN- 1.22016214 0.02217895 1097 UTRN- 30am002fDMD 144 qRTPCR 44 m01 16 195707 UTRN- 1.17726461 0.01617406 1097UTRN- 30 am002fDMD 144 qRTPCR 45 m01 16 422943 UTRN- 1.219316090.05796389 1097 UTRN- 30 am002fDMD 144 qRTPCR 46 m01 16 422946 UTRN-1.09650056 0.07741785 1097 UTRN- 30 am002fDMD 144 qRTPCR 47 m01 16210674 UTRN- 1.19915402 0.0338564 1097 UTRN- 30 am002fDMD 144 qRTPCR 48m01 16 426032 UTRN- 1.1321997 0.03432322 1097 UTRN- 30 am002fDMD 144qRTPCR 49 m01 16 225629 UTRN- 1.17482362 0.07479833 1097 UTRN- 30am002fDMD 144 qRTPCR 50 m01 16 225662 UTRN- 0.86280779 0.0230224 1097UTRN- 30 am002fDMD 144 qRTPCR 51 m01 16 229456 UTRN- 1.100250110.0429719 1097 UTRN- 30 am002fDMD 144 qRTPCR 52 m01 16 436557 UTRN-1.01849372 0.02944671 1097 UTRN- 30 am002fDMD 144 qRTPCR 53 m01 16238467 UTRN- 0.93011546 0.050621216 1097 UTRN- 30 am002fDMD 144 qRTPCR54 m01 16 242264 UTRN- 0.9285505 0.02965249 1097 UTRN- 30 am002fDMD 144qRTPCR 55 m01 16 251939 UTRN- 1.02614832 0.05760928 1097 UTRN- 30am002fDMD 144 qRTPCR 56 m01 16 453443 UTRN- 0.99500772 0.00717961 1097UTRN- 30 am002fDMD 144 qRTPCR 57 m01 16 453483 UTRN- 1.034683660.03962052 1097 UTRN- 30 am002fDMD 144 qRTPCR 58 m01 16 456038 UTRN-1.00688925 0.04965703 1097 UTRN- 30 am002fDMD 144 qRTPCR 59 m01 16272301 UTRN- 0.9921631 0.01799872 1097 UTRN- 30 am002fDMD 144 qRTPCR 60m01 16 Ctrl Un 1.08692556 0.04802467 1097 UTRN- 30 am002fDMD 144 qRTPCR16 Ctrl 1 0.04148875 1097 UTRN- 30 am002fDMD 144 qRTPCR Lipo 16 276749UTRN- 0.95657363 0.07952758 1097 UTRN- 30 am002fDMD 144 qRTPCR 61 m01 16289697 UTRN- 1.27556793 0.08315062 1097 UTRN- 30 am002fDMD 144 qRTPCR 62m01 16 292490 UTRN- 1.16339533 0.08677085 1097 UTRN- 30 am002fDMD 144qRTPCR 63 m01 16 292535 UTRN- 1.36654512 0.04898731 1097 UTRN- 30am002fDMD 144 qRTPCR 64 m01 16 292541 UTRN- 0.86254085 0.06740933 1097UTRN- 30 am002fDMD 144 qRTPCR 65 m01 16 Ctrl 1 0.07402642 1097 UTRN- 30am002fDMD 144 qRTPCR Lipo 16 Ctrl Un 1.69636888 0.10587351 1097 UTRN- 30am002fDMD 144 qRTPCR 16 313770 UTRN- 0.58076529 0.03039882 1098 UTRN- 30am002fDMD 96 qRTPCR 01 m01 16 5776 UTRN- 0.96881503 0.08147278 1098UTRN- 30 am002fDMD 96 qRTPCR 02 m01 16 5781 UTRN- 0.8233217 0.040113161098 UTRN- 30 am002fDMD 96 qRTPCR 03 m01 16 32192 UTRN- 1.166713250.06652984 1098 UTRN- 30 am002fDMD 96 qRTPCR 04 m01 16 39558 UTRN-0.80244274 0.03208655 1098 UTRN- 30 am002fDMD 96 qRTPCR 05 m01 16 45784UTRN- 1.1712878 0.03151455 1098 UTRN- 30 am002fDMD 96 qRTPCR 06 m01 1660002 UTRN- 0.89575232 0.02762414 1098 UTRN- 30 am002fDMD 96 qRTPCR 07m01 16 60035 UTRN- 0.5689325 0.01841599 1098 UTRN- 30 am002fDMD 96qRTPCR 08 m01 16 60038 UTRN- 0.46116762 0.02018062 1098 UTRN- 30am002fDMD 96 qRTPCR 09 m01 16 336679 UTRN- 0.59071506 0.02036091 1098UTRN- 30 am002fDMD 96 qRTPCR 10 m01 16 62709 UTRN- 0.45292364 0.056210241098 UTRN- 30 am002fDMD 96 qRTPCR 11 m01 16 64394 UTRN- 0.590369330.02970165 1098 UTRN- 30 am002fDMD 96 qRTPCR 12 m01 16 64407 UTRN-0.47978013 0.04345336 1098 UTRN- 30 am002fDMD 96 qRTPCR 13 m01 16 68368UTRN- 1.09580674 0.02423345 1098 UTRN- 30 am002fDMD 96 qRTPCR 14 m01 1668420 UTRN- 0.74264079 0.03365387 1098 UTRN- 30 am002fDMD 96 qRTPCR 15m01 16 68424 UTRN- 0.87712391 0.05397445 1098 UTRN- 30 am002fDMD 96qRTPCR 16 m01 16 82947 UTRN- 1.08253115 0.02494187 1098 UTRN- 30am002fDMD 96 qRTPCR 17 m01 16 85204 UTRN- 0.76472603 0.03441017 1098UTRN- 30 am002fDMD 96 qRTPCR 18 m01 16 89541 UTRN- 0.4453413 0.022997611098 UTRN- 30 am002fDMD 96 qRTPCR 19 m01 16 355024 UTRN- 0.796038480.06100838 1098 UTRN- 30 am002fDMD 96 qRTPCR 20 m01 16 99210 UTRN-0.55112051 0.01090463 1098 UTRN- 30 am002fDMD 96 qRTPCR 21 m01 16 101919UTRN- 1.10907773 0.01134182 1098 UTRN- 30 am002fDMD 96 qRTPCR 22 m01 16101994 UTRN- 0.7410306 0.04264853 1098 UTRN- 30 am002fDMD 96 qRTPCR 23m01 16 103832 UTRN- 1.19776254 0.04344756 1098 UTRN- 30 am002fDMD 96qRTPCR 24 m01 16 103833 UTRN- 1.40237149 0.04131397 1098 UTRN- 30am002fDMD 96 qRTPCR 25 m01 16 103853 UTRN- 0.88496235 0.02236041 1098UTRN- 30 am002fDMD 96 qRTPCR 26 m01 16 103933 UTRN- 0.512598210.02670704 1098 UTRN- 30 am002fDMD 96 qRTPCR 27 m01 16 117420 UTRN-0.85318924 0.01188527 1098 UTRN- 30 am002fDMD 96 qRTPCR 28 m01 16 120115UTRN- 1.4078235 0.0069635 1098 UTRN- 30 am002fDMD 96 qRTPCR 29 m01 16120121 UTRN- 0.97599956 0.03751087 1098 UTRN- 30 am002fDMD 96 qRTPCR 30m01 16 Ctrl Un 1.05179276 0.06427556 1098 UTRN- 30 am002fDMD 96 qRTPCR16 Ctrl 1 0.07413322 1098 UTRN- 30 am002fDMD 96 qRTPCR Lipo 16 362061UTRN- 0.87482409 0.03160046 1098 UTRN- 30 am002fDMD 96 qRTPCR 31 m01 16372488 UTRN- 0.90578907 0.04281746 1098 UTRN- 30 am002fDMD 96 qRTPCR 32m01 16 372542 UTRN- 0.79508229 0.04767849 1098 UTRN- 30 am002fDMD 96qRTPCR 33 m01 16 376352 UTRN- 1.12394667 0.10893678 1098 UTRN- 30am002fDMD 96 qRTPCR 34 m01 16 139243 UTRN- 0.63887247 0.02591518 1098UTRN- 30 am002fDMD 96 qRTPCR 35 m01 16 143189 UTRN- 1.021558850.07088794 1098 UTRN- 30 am002fDMD 96 qRTPCR 36 m01 16 151630 UTRN-0.70881548 0.06529816 1098 UTRN- 30 am002fDMD 96 qRTPCR 37 m01 16 166370UTRN- 0.50209162 0.03139329 1098 UTRN- 30 am002fDMD 96 qRTPCR 38 m01 16166372 UTRN- 0.82631739 0.00543354 1098 UTRN- 30 am002fDMD 96 qRTPCR 39m01 16 169368 UTRN- 0.87845259 0.02260314 1098 UTRN- 30 am002fDMD 96qRTPCR 40 m01 16 399345 UTRN- 0.70623726 0.01080899 1098 UTRN- 30am002fDMD 96 qRTPCR 41 m01 16 412519 UTRN- 1.01312974 0.03339384 1098UTRN- 30 am002fDMD 96 qRTPCR 42 m01 16 412600 UTRN- 0.920729920.04505221 1098 UTRN- 30 am002fDMD 96 qRTPCR 43 m01 16 414862 UTRN-0.57355729 0.03685588 1098 UTRN- 30 am002fDMD 96 qRTPCR 44 m01 16 195707UTRN- 0.79911892 0.01900042 1098 UTRN- 30 am002fDMD 96 qRTPCR 45 m01 16422943 UTRN- 0.93613873 0.01779705 1098 UTRN- 30 am002fDMD 96 qRTPCR 46m01 16 422946 UTRN- 0.4587612 0.02411369 1098 UTRN- 30 am002fDMD 96qRTPCR 47 m01 16 210674 UTRN- 0.74859068 0.02362965 1098 UTRN- 30am002fDMD 96 qRTPCR 48 m01 16 426032 UTRN- 0.66580214 0.02139001 1098UTRN- 30 am002fDMD 96 qRTPCR 49 m01 16 225629 UTRN- 0.830196270.02025208 1098 UTRN- 30 am002fDMD 96 qRTPCR 50 m01 16 225662 UTRN-0.46833508 0.01039709 1098 UTRN- 30 am002fDMD 96 qRTPCR 51 m01 16 229456UTRN- 0.70892642 0.00242912 1098 UTRN- 30 am002fDMD 96 qRTPCR 52 m01 16436557 UTRN- 0.64888575 0.03688872 1098 UTRN- 30 am002fDMD 96 qRTPCR 53m01 16 238467 UTRN- 0.8529075 0.03343083 1098 UTRN- 30 am002fDMD 96qRTPCR 54 m01 16 242264 UTRN- 0.52305543 0.04356075 1098 UTRN- 30am002fDMD 96 qRTPCR 55 m01 16 251939 UTRN- 0.66743863 0.05307766 1098UTRN- 30 am002fDMD 96 qRTPCR 56 m01 16 453443 UTRN- 0.910132960.06546661 1098 UTRN- 30 am002fDMD 96 qRTPCR 57 m01 16 453483 UTRN-0.6125509 0.02627138 1098 UTRN- 30 am002fDMD 96 qRTPCR 58 m01 16 456038UTRN- 0.99789605 0.06465815 1098 UTRN- 30 am002fDMD 96 qRTPCR 59 m01 16272301 UTRN- 0.91755307 0.06594373 1098 UTRN- 30 am002fDMD 96 qRTPCR 60m01 16 Ctrl Un 0.89152675 0.0402528 1098 UTRN- 30 am002fDMD 96 qRTPCR 16Ctrl 1 0.06455142 1098 UTRN- 30 am002fDMD 96 qRTPCR Lipo 16 276749 UTRN-0.67867922 0.02399703 1098 UTRN- 30 am002fDMD 96 qRTPCR 61 m01 16 289697UTRN- 1.04840944 0.02365808 1098 UTRN- 30 am002fDMD 96 qRTPCR 62 m01 16292490 UTRN- 1.00338618 0.0808448 1098 UTRN- 30 am002fDMD 96 qRTPCR 63m01 16 292535 UTRN- 0.77127007 0.03101058 1098 UTRN- 30 am002fDMD 96qRTPCR 64 m01 16 292541 UTRN- 0.59484854 0.0342936 1098 UTRN- 30am002fDMD 96 qRTPCR 65 m01 16 Ctrl 1 0.09383278 1098 UTRN- 30 am002fDMD96 qRTPCR Lipo 16 Ctrl Un 0.95433212 0.05764991 1098 UTRN- 30 am002fDMD96 qRTPCR 16 313770 UTRN- 1.09999355 0.0522105 1099 UTRN- 50 am002fDMD16 qRTPCR 01 m01 16 5776 UTRN- 0.98048522 0.05829249 1099 UTRN- 50am002fDMD 16 qRTPCR 02 m01 16 5781 UTRN- 1.11018609 0.09057436 1099UTRN- 50 am002fDMD 16 qRTPCR 03 m01 16 32192 UTRN- 1.04324326 0.058745481099 UTRN- 50 am002fDMD 16 qRTPCR 04 m01 16 39558 UTRN- 0.902673370.02384534 1099 UTRN- 50 am002fDMD 16 qRTPCR 05 m01 16 45784 UTRN-0.95957965 0.02440134 1099 UTRN- 50 am002fDMD 16 qRTPCR 06 m01 16 60002UTRN- 1.06633244 0.06683347 1099 UTRN- 50 am002fDMD 16 qRTPCR 07 m01 1660035 UTRN- 1.03379791 0.07644067 1099 UTRN- 50 am002fDMD 16 qRTPCR 08m01 16 60038 UTRN- 1.19128452 0.06345743 1099 UTRN- 50 am002fDMD 16qRTPCR 09 m01 16 336679 UTRN- 1.04590735 0.02568251 1099 UTRN- 50am002fDMD 16 qRTPCR 10 m01 16 62709 UTRN- 1.3006283 0.09566221 1099UTRN- 50 am002fDMD 16 qRTPCR 11 m01 16 64394 UTRN- 1.32164316 0.073367191099 UTRN- 50 am002fDMD 16 qRTPCR 12 m01 16 64407 UTRN- 1.024577350.0099744 1099 UTRN- 50 am002fDMD 16 qRTPCR 13 m01 16 68368 UTRN-0.89786302 0.02932433 1099 UTRN- 50 am002fDMD 16 qRTPCR 14 m01 16 68420UTRN- 1.04929606 0.02858814 1099 UTRN- 50 am002fDMD 16 qRTPCR 15 m01 1668424 UTRN- 1.0167624 0.04978825 1099 UTRN- 50 am002fDMD 16 qRTPCR 16m01 16 82947 UTRN- 1.33820211 0.16165828 1099 UTRN- 50 am002fDMD 16qRTPCR 17 m01 16 85204 UTRN- 1.08174251 0.03029958 1099 UTRN- 50am002fDMD 16 qRTPCR 18 m01 16 89541 UTRN- 1.2124862 0.03538288 1099UTRN- 50 am002fDMD 16 qRTPCR 19 m01 16 355024 UTRN- 1.187078080.08658924 1099 UTRN- 50 am002fDMD 16 qRTPCR 20 m01 16 99210 UTRN-1.06985407 0.00459959 1099 UTRN- 50 am002fDMD 16 qRTPCR 21 m01 16 101919UTRN- 1.02001321 0.00982358 1099 UTRN- 50 am002fDMD 16 qRTPCR 22 m01 16101994 UTRN- 1.07309486 0.03530298 1099 UTRN- 50 am002fDMD 16 qRTPCR 23m01 16 103832 UTRN- 1.15223004 0.02317344 1099 UTRN- 50 am002fDMD 16qRTPCR 24 m01 16 103833 UTRN- 1.07729047 0.08903163 1099 UTRN- 50am002fDMD 16 qRTPCR 25 m01 16 103853 UTRN- 1.05670588 0.03993355 1099UTRN- 50 am002fDMD 16 qRTPCR 26 m01 16 103933 UTRN- 0.922302390.13830922 1099 UTRN- 50 am002fDMD 16 qRTPCR 27 m01 16 117420 UTRN-1.0269754 0.18269877 1099 UTRN- 50 am002fDMD 16 qRTPCR 28 m01 16 120115UTRN- 0.95740501 0.13717197 1099 UTRN- 50 am002fDMD 16 qRTPCR 29 m01 16120121 UTRN- 0.91015254 0.01477685 1099 UTRN- 50 am002fDMD 16 qRTPCR 30m01 16 Ctrl Un 1.17147479 0.06069851 1099 UTRN- 50 am002fDMD 16 qRTPCR16 Ctrl 1 0.01155989 1099 UTRN- 50 am002fDMD 16 qRTPCR Lipo 16 362061UTRN- 0.84129209 0.0551895 1099 UTRN- 50 am002fDMD 16 qRTPCR 31 m01 16372488 UTRN- 0.87401238 0.05711907 1099 UTRN- 50 am002fDMD 16 qRTPCR 32m01 16 372542 UTRN- 1.00773219 0.136912 1099 UTRN- 50 am002fDMD 16qRTPCR 33 m01 16 376352 UTRN- 0.88581399 0.08839522 1099 UTRN- 50am002fDMD 16 qRTPCR 34 m01 16 139243 UTRN- 0.81977584 0.0747876 1099UTRN- 50 am002fDMD 16 qRTPCR 35 m01 16 143189 UTRN- 0.90303543 0.06395271099 UTRN- 50 am002fDMD 16 qRTPCR 36 m01 16 151630 UTRN- 0.858522050.06571187 1099 UTRN- 50 am002fDMD 16 qRTPCR 37 m01 16 166370 UTRN-0.79791465 0.04599394 1099 UTRN- 50 am002fDMD 16 qRTPCR 38 m01 16 166372UTRN- 0.70577426 0.02258757 1099 UTRN- 50 am002fDMD 16 qRTPCR 39 m01 16169368 UTRN- 0.86132342 0.07520493 1099 UTRN- 50 am002fDMD 16 qRTPCR 40m01 16 399345 UTRN- 0.95686499 0.04826801 1099 UTRN- 50 am002fDMD 16qRTPCR 41 m01 16 412519 UTRN- 0.91846716 0.06735625 1099 UTRN- 50am002fDMD 16 qRTPCR 42 m01 16 412600 UTRN- 0.90545962 0.0764699 1099UTRN- 50 am002fDMD 16 qRTPCR 43 m01 16 414862 UTRN- 0.872503140.04934873 1099 UTRN- 50 am002fDMD 16 qRTPCR 44 m01 16 195707 UTRN-0.90958 0.0321877 1099 UTRN- 50 am002fDMD 16 qRTPCR 45 m01 16 422943UTRN- 0.77236631 0.02358972 1099 UTRN- 50 am002fDMD 16 qRTPCR 46 m01 16422946 UTRN- 0.79566678 0.0195359 1099 UTRN- 50 am002fDMD 16 qRTPCR 47m01 16 210674 UTRN- 0.92591552 0.0686307 1099 UTRN- 50 am002fDMD 16qRTPCR 48 m01 16 426032 UTRN- 0.91753186 0.11107633 1099 UTRN- 50am002fDMD 16 qRTPCR 49 m01 16 225629 UTRN- 0.90366093 0.05020314 1099UTRN- 50 am002fDMD 16 qRTPCR 50 m01 16 225662 UTRN- 0.847737630.01225047 1099 UTRN- 50 am002fDMD 16 qRTPCR 51 m01 16 229456 UTRN-0.93886586 0.03206633 1099 UTRN- 50 am002fDMD 16 qRTPCR 52 m01 16 436557UTRN- 0.99264254 0.07123769 1099 UTRN- 50 am002fDMD 16 qRTPCR 53 m01 16238467 UTRN- 0.78797951 0.05217497 1099 UTRN- 50 am002fDMD 16 qRTPCR 54m01 16 242264 UTRN- 0.77050873 0.04398832 1099 UTRN- 50 am002fDMD 16qRTPCR 55 m01 16 251939 UTRN- 0.89266966 0.05871496 1099 UTRN- 50am002fDMD 16 qRTPCR 56 m01 16 453443 UTRN- 0.92906018 0.07248755 1099UTRN- 50 am002fDMD 16 qRTPCR 57 m01 16 453483 UTRN- 0.944970210.04599071 1099 UTRN- 50 am002fDMD 16 qRTPCR 58 m01 16 456038 UTRN-0.94970793 0.0624258 1099 UTRN- 50 am002fDMD 16 qRTPCR 59 m01 16 272301UTRN- 0.8175283 0.00629294 1099 UTRN- 50 am002fDMD 16 qRTPCR 60 m01 16Ctrl Un 0.8823963 0.05212196 1099 UTRN- 50 am002fDMD 16 qRTPCR 16 Ctrl 10.11512636 1099 UTRN- 50 am002fDMD 16 qRTPCR Lipo 16 276749 UTRN-0.84129209 0.0551895 1099 UTRN- 50 am002fDMD 16 qRTPCR 61 m01 16 289697UTRN- 0.87401238 0.05711907 1099 UTRN- 50 am002fDMD 16 qRTPCR 62 m01 16292490 UTRN- 1.00773219 0.136912 1099 UTRN- 50 am002fDMD 16 qRTPCR 63m01 16 292535 UTRN- 0.88581399 0.08839522 1099 UTRN- 50 am002fDMD 16qRTPCR 64 m01 16 292541 UTRN- 0.81977584 0.0747876 1099 UTRN- 50am002fDMD 16 qRTPCR 65 m01 16 497808 unc- 0.90303543 0.0639527 1099UTRN- 50 am002fDMD 16 qRTPCR 232 16 m12 497809 unc- 0.858522050.06571187 1099 UTRN- 50 am002fDMD 16 qRTPCR 293 16 m12 497808 unc-0.79791465 0.04599394 1099 UTRN- 50 am002fDMD 16 qRTPCR 232 16 m01497809 unc- 0.70577426 0.02258757 1099 UTRN- 50 am002fDMD 16 qRTPCR 29316 m01 Ctrl Un 0.8823963 0.05212196 1099 UTRN- 50 am002fDMD 16 qRTPCR 16Ctrl 1 0.11512636 1099 UTRN- 50 am002fDMD 16 qRTPCR Lipo 16

TABLE 4 Formatted sequences OligoID Base Sequence Formatted SequenceSeqID UTRN-01 CATCGTAGGAAGInaCs; omeAs; InaTs; omeCs; InaGs; omeUs; InaAs; omeGs; 313770 m01 TTGInaGs; omeAs; InaAs; omeGs; InaTs; omeUs; InaG-Sup UTRN-02 CCGGTATCATGGInaCs; omeCs; InaGs; omeGs; InaTs; omeAs; InaTs; omeCs; 5776 m01 AGGInaAs; omeUs; InaGs; omeGs; InaAs; omeGs; InaG-Sup UTRN-03 CAACACCGGTATInaCs; omeAs; InaAs; omeCs; InaAs; omeCs; InaCs; omeGs; 5781 m01 CATInaGs; omeUs; InaAs; omeUs; InaCs; omeAs; InaT-Sup UTRN-04 CCGAACATCACCCInaCs; omeCs; InaGs; omeAs; InaAs; omeCs; InaAs; omeUs; 32192 m01 ACInaCs; omeAs; InaCs; omeCs; InaCs; omeAs; InaC-Sup UTRN-05 GGACTTCTGGACInaGs; omeGs; InaAs; omeCs; InaTs; omeUs; InaCs; omeUs; 39558 m01 GACInaGs; omeGs; InaAs; omeCs; InaGs; omeAs; InaC-Sup UTRN-06 CCAAAACCTAGCInaCs; omeCs; InaAs; omeAs; InaAs; omeAs; InaCs; omeCs; 45784 m01 GTTInaTs; omeAs; InaGs; omeCs; InaGs; omeUs; InaT-Sup UTRN-07 CTTTTGTGACGTCInaCs; omeUs; InaTs; omeUs; InaTs; omeGs; InaTs; omeGs; 60002 m01 CCInaAs; omeCs; InaGs; omeUs; InaCs; omeCs; InaC-Sup UTRN-08 CCCGATATGATGInaCs; omeCs; InaCs; omeGs; InaAs; omeUs; InaAs; omeUs; 60035 m01 CACInaGs; omeAs; InaTs; omeGs; InaCs; omeAs; InaC-Sup UTRN-09 ATCCCCGATATGAInaAs; omeUs; InaCs; omeCs; InaCs; omeCs; InaGs; omeAs; 60038 m01 TGInaTs; omeAs; InaTs; omeGs; InaAs; omeUs; InaG-Sup UTRN-10 CCACCGACATAAInaCs; omeCs; InaAs; omeCs; InaCs; omeGs; InaAs; omeCs; 336679 m01 GTGInaAs; omeUs; InaAs; omeAs; InaGs; omeUs; InaG-Sup UTRN-11 CTCTCCGATGCCAInaCs; omeUs; InaCs; omeUs; InaCs; omeCs; InaGs; omeAs; 62709 m01 AGInaTs; omeGs; InaCs; omeCs; InaAs; omeAs; InaG-Sup UTRN-12 GGCGTCTATGGTInaGs; omeGs; InaCs; omeGs; InaTs; omeCs; InaTs; omeAs; 64394 m01 GACInaTs; omeGs; InaGs; omeUs; InaGs; omeAs; InaC-Sup UTRN-13 CTACCTCACGGATInaCs; omeUs; InaAs; omeCs; InaCs; omeUs; InaCs; omeAs; 64407 m01 GGInaCs; omeGs; InaGs; omeAs; InaTs; omeGs; InaG-Sup UTRN-14 GAGTTTCAGCTCInaGs; omeAs; InaGs; omeUs; InaTs; omeUs; InaCs; omeAs; 68368 m01 GGGInaGs; omeCs; InaTs; omeCs; InaGs; omeGs; InaG-Sup UTRN-15 AACGCAATCTGAInaAs; omeAs; InaCs; omeGs; InaCs; omeAs; InaAs; omeUs; 68420 m01 TAGInaCs; omeUs; InaGs; omeAs; InaTs; omeAs; InaG-Sup UTRN-16 CTCCAACGCAATCInaCs; omeUs; InaCs; omeCs; InaAs; omeAs; InaCs; omeGs; 68424 m01 TGInaCs; omeAs; InaAs; omeUs; InaCs; omeUs; InaG-Sup UTRN-17 CATTTCGGAAGTInaCs; omeAs; InaTs; omeUs; InaTs; omeCs; InaGs; omeGs; 82947 m01 GTCInaAs; omeAs; InaGs; omeUs; InaGs; omeUs; InaC-Sup UTRN-18 TTATTCGATGCCAInaTs; omeUs; InaAs; omeUs; InaTs; omeCs; InaGs; omeAs; 85204 m01 CCInaTs; omeGs; InaCs; omeCs; InaAs; omeCs; InaC-Sup UTRN-19 CAATTCCCGCTAAInaCs; omeAs; InaAs; omeUs; InaTs; omeCs; InaCs; omeCs; 89541 m01 GGInaGs; omeCs; InaTs; omeAs; InaAs; omeGs; InaG-Sup UTRN-20 CTAATCTTCGAAGInaCs; omeUs; InaAs; omeAs; InaTs; omeCs; InaTs; omeUs; 355024 m01 TGInaCs; omeGs; InaAs; omeAs; InaGs; omeUs; InaG-Sup UTRN-21 CTCGAATTCTATTInaCs; omeUs; InaCs; omeGs; InaAs; omeAs; InaTs; omeUs; 99210 m01 ACInaCs; omeUs; InaAs; omeUs; InaTs; omeAs; InaC-Sup UTRN-22 GGAGATCACGGGInaGs; omeGs; InaAs; omeGs; InaAs; omeUs; InaCs; omeAs; 101919 m01 TTCInaCs; omeGs; InaGs; omeGs; InaTs; omeUs; InaC-Sup UTRN-23 CATTTGCCTGCGTInaCs; omeAs; InaTs; omeUs; InaTs; omeGs; InaCs; omeCs; 101994 m01 AAInaTs; omeGs; InaCs; omeGs; InaTs; omeAs; InaA-Sup UTRN-24 CGATTATCTGCCGInaCs; omeGs; InaAs; omeUs; InaTs; omeAs; InaTs; omeCs; 103832 m01 GGInaTs; omeGs; InaCs; omeCs; InaGs; omeGs; InaG-Sup UTRN-25 GCGATTATCTGCCInaGs; omeCs; InaGs; omeAs; InaTs; omeUs; InaAs; omeUs; 103833 m01 GGInaCs; omeUs; InaGs; omeCs; InaCs; omeGs; InaG-Sup UTRN-26 CCAAGCTCTCGAInaCs; omeCs; InaAs; omeAs; InaGs; omeCs; InaTs; omeCs; 103853 m01 ATCInaTs; omeCs; InaGs; omeAs; InaAs; omeUs; InaC-Sup UTRN-27 GATCTTCATATCGInaGs; omeAs; InaTs; omeCs; InaTs; omeUs; InaCs; omeAs; 103933 m01 GCInaTs; omeAs; InaTs; omeCs; InaGs; omeGs; InaC-Sup UTRN-28 CAGGTACGAACTInaCs; omeAs; InaGs; omeGs; InaTs; omeAs; InaCs; omeGs; 117420 m01 CGGInaAs; omeAs; InaCs; omeUs; InaCs; omeGs; InaG-Sup UTRN-29 GCGTTACTGATGTInaGs; omeCs; InaGs; omeUs; InaTs; omeAs; InaCs; omeUs; 120115 m01 CTInaGs; omeAs; InaTs; omeGs; InaTs; omeCs; InaT-Sup UTRN-30 CCAAAAGCGTTAInaCs; omeCs; InaAs; omeAs; InaAs; omeAs; InaGs; omeCs; 120121 m01 CTGInaGs; omeUs; InaTs; omeAs; InaCs; omeUs; InaG-Sup UTRN-31 TTTAAACCAACGCInaTs; omeUs; InaTs; omeAs; InaAs; omeAs; InaCs; omeCs; 362061 m01 TGInaAs; omeAs; InaCs; omeGs; InaCs; omeUs; InaG-Sup UTRN-32 CACCGATCTGCATInaCs; omeAs; InaCs; omeCs; InaGs; omeAs; InaTs; omeCs; 372488 m01 TCInaTs; omeGs; InaCs; omeAs; InaTs; omeUs; InaC-Sup UTRN-33 GGAGTCATACGAInaGs; omeGs; InaAs; omeGs; InaTs; omeCs; InaAs; omeUs; 372542 m01 TGCInaAs; omeCs; InaGs; omeAs; InaTs; omeGs; InaC-Sup UTRN-34 CTCATGATAACCGInaCs; omeUs; InaCs; omeAs; InaTs; omeGs; InaAs; omeUs; 376352 m01 TGInaAs; omeAs; InaCs; omeCs; InaGs; omeUs; InaG-Sup UTRN-35 GAATATAGAGTCInaGs; omeAs; InaAs; omeUs; InaAs; omeUs; InaAs; omeGs; 139243 m01 GAGInaAs; omeGs; InaTs; omeCs; InaGs; omeAs; InaG-Sup UTRN-36 CCAATTCGGTGAInaCs; omeCs; InaAs; omeAs; InaTs; omeUs; InaCs; omeGs; 143189 m01 ATGInaGs; omeUs; InaGs; omeAs; InaAs; omeUs; InaG-Sup UTRN-37 CCCATCTACATACInaCs; omeCs; InaCs; omeAs; InaTs; omeCs; InaTs; omeAs;  151630 m01 GCInaCs; omeAs; InaTs; omeAs; InaCs; omeGs; InaC-Sup UTRN-38 CCGATTAATTTACInaCs; omeCs; InaGs; omeAs; InaTs; omeUs; InaAs; omeAs; 166370 m01 CCInaTs; omeUs; InaTs; omeAs; InaCs; omeCs; InaC-Sup UTRN-39 CCCCGATTAATTTInaCs; omeCs; InaCs; omeCs; InaGs; omeAs; InaTs; omeUs; 166372 m01 ACInaAs; omeAs; InaTs; omeUs; InaTs; omeAs; InaC-Sup UTRN-40 AATGAAACAGCGInaAs; omeAs; InaTs; omeGs; InaAs; omeAs; InaAs; omeCs; 169368 m01 TAGInaAs; omeGs; InaCs; omeGs; InaTs; omeAs; InaG-Sup UTRN-41 CTGAGTTATCGTAInaCs; omeUs; InaGs; omeAs; InaGs; omeUs; InaTs; omeAs; 399345 m01 AAInaTs; omeCs; InaGs; omeUs; InaAs; omeAs; InaA-Sup UTRN-42 AGAAGTTAAACGInaAs; omeGs; InaAs; omeAs; InaGs; omeUs; InaTs; omeAs; 412519 m01 CTGInaAs; omeAs; InaCs; omeGs; InaCs; omeUs; InaG-Sup UTRN-43 CTTCAACTTACGGInaCs; omeUs; InaTs; omeCs; InaAs; omeAs; InaCs; omeUs; 412600 m01 GAInaTs; omeAs; InaCs; omeGs; InaGs; omeGs; InaA-Sup UTRN-44 GCCTTAACGATTTInaGs; omeCs; InaCs; omeUs; InaTs; omeAs; InaAs; omeCs; 414862 m01 ACInaGs; omeAs; InaTs; omeUs; InaTs; omeAs; InaC-Sup UTRN-45 CTGTTTCCGTCAAInaCs; omeUs; InaGs; omeUs; InaTs; omeUs; InaCs; omeCs; 195707 m01 TGInaGs; omeUs; InaCs; omeAs; InaAs; omeUs; InaG-Sup UTRN-46 TGAGTCGCTTAATInaTs; omeGs; InaAs; omeGs; InaTs; omeCs; InaGs; omeCs; 422943 m01 TCInaTs; omeUs; InaAs; omeAs; InaTs; omeUs; InaC-Sup UTRN-47 GTCGCTTAATTCAInaGs; omeUs; InaCs; omeGs; InaCs; omeUs; InaTs; omeAs; 422946 m01 AAInaAs; omeUs; InaTs; omeCs; InaAs; omeAs; InaA-Sup UTRN-48 CTAAGGCGAAATInaCs; omeUs; InaAs; omeAs; InaGs; omeGs; InaCs; omeGs; 210674 m01 CTCInaAs; omeAs; InaAs; omeUs; InaCs; omeUs; InaC-Sup UTRN-49 CTCGGACTCTACTInaCs; omeUs; InaCs; omeGs; InaGs; omeAs; InaCs; omeUs; 426032 m01 TGInaCs; omeUs; InaAs; omeCs; InaTs; omeUs; InaG-Sup UTRN-50 CTTTAACTCCCGTInaCs; omeUs; InaTs; omeUs; InaAs; omeAs; InaCs; omeUs; 225629 m01 CTInaCs; omeCs; InaCs; omeGs; InaTs; omeCs; InaT-Sup UTRN-51 GTCGACAGCATTInaGs; omeUs; InaCs; omeGs; InaAs; omeCs; InaAs; omeGs; 225662 m01 CAGInaCs; omeAs; InaTs; omeUs; InaCs; omeAs; InaG-Sup UTRN-52 TTTACCCAATCGAInaTs; omeUs; InaTs; omeAs; InaCs; omeCs; InaCs; omeAs; 229456 m01 TGInaAs; omeUs; InaCs; omeGs; InaAs; omeUs; InaG-Sup UTRN-53 GTAGCTCGATCAInaGs; omeUs; InaAs; omeGs; InaCs; omeUs; InaCs; omeGs; 436557 m01 ATCInaAs; omeUs; InaCs; omeAs; InaAs; omeUs; InaC-Sup UTRN-54 CATCTAGCTGGCInaCs; omeAs; InaTs; omeCs; InaTs; omeAs; InaGs; omeCs; 238467 m01 GAGInaTs; omeGs; InaGs; omeCs; InaGs; omeAs; InaG-Sup UTRN-55 GGATCTTTGCCACInaGs; omeGs; InaAs; omeUs; InaCs; omeUs; InaTs; omeUs; 242264 m01 GGInaGs; omeCs; InaCs; omeAs; InaCs; omeGs; InaG-Sup UTRN-56 ACGACAACAGTAInaAs; omeCs; InaGs; omeAs; InaCs; omeAs; InaAs; omeCs; 251939 m01 CTGInaAs; omeGs; InaTs; omeAs; InaCs; omeUs; InaG-Sup UTRN-57 CTGAATAATGTACInaCs; omeUs; InaGs; omeAs; InaAs; omeUs; InaAs; omeAs; 453443 m01 GTInaTs; omeGs; InaTs; omeAs; InaCs; omeGs; InaT-Sup UTRN-58 AAATCCGAAGACInaAs; omeAs; InaAs; omeUs; InaCs; omeCs; InaGs; omeAs; 453483 m01 TACInaAs; omeGs; InaAs; omeCs; InaTs; omeAs; InaC-Sup UTRN-59 GTTGTCGATCACCInaGs; omeUs; InaTs; omeGs; InaTs; omeCs; InaGs; omeAs; 456038 m01 TCInaTs; omeCs; InaAs; omeCs; InaCs; omeUs; InaC-Sup UTRN-60 CTATTAAGTAGCCInaCs; omeUs; InaAs; omeUs; InaTs; omeAs; InaAs; omeGs; 272301 m01 GTInaTs; omeAs; InaGs; omeCs; InaCs; omeGs; InaT-Sup UTRN-61 GTAACCAAGTCGInaGs; omeUs; InaAs; omeAs; InaCs; omeCs; InaAs; omeAs; 276749 m01 AGGInaGs; omeUs; InaCs; omeGs; InaAs; omeGs; InaG-Sup UTRN-62 CAGACGTGTGATInaCs; omeAs; InaGs; omeAs; InaCs; omeGs; InaTs; omeGs; 289697 m01 GGGInaTs; omeGs; InaAs; omeUs; InaGs; omeGs; InaG-Sup UTRN-63 CACCATTGATTCGInaCs; omeAs; InaCs; omeCs; InaAs; omeUs; InaTs; omeGs; 292490 m01 GGInaAs; omeUs; InaTs; omeCs; InaGs; omeGs; InaG-Sup UTRN-64 GCGAGTAGCTCAInaGs; omeCs; InaGs; omeAs; InaGs; omeUs; InaAs; omeGs; 292535 m01 GTGInaCs; omeUs; InaCs; omeAs; InaGs; omeUs; InaG-Sup UTRN-65 GATCAAGCGAGTInaGs; omeAs; InaTs; omeCs; InaAs; omeAs; InaGs; omeCs; 292541 m01 AGCInaGs; omeAs; InaGs; omeUs; InaAs; omeGs; InaC-Sup UTRN- CCCCGATCTATTCInaCs; InaCs; InaCs; dCs; dGs; dAs; dTs; dCs; dTs; dAs; dTs; dTs; 497729112 m08 TC InaCs; InaTs; InaC-Sup UTRN- CCCGATCTATTCTInaCs; InaCs; InaCs; dGs; dAs; dTs; dCs; dTs; dAs; dTs; dTs; dCs; 497730113 m08 CC InaTs; InaCs; InaC-Sup UTRN- CCGATCTATTCTCInaCs; InaCs; InaGs; dAs; dTs; dCs; dTs; dAs; dTs; dTs; dCs; dTs; 497731114 m08 CA InaCs; InaCs; InaA-Sup UTRN- GCGCGATGCTGAInaGs; InaCs; InaGs; dCs; dGs; dAs; dTs; dGs; dCs; dTs; dGs; dAs; 497732115 m08 ACT InaAs; InaCs; InaT-Sup UTRN- CTGCGAACAGCAInaCs; InaTs; InaGs; dCs; dGs; dAs; dAs; dCs; dAs; dGs; dCs; dAs; 497733116 m08 ATG InaAs; InaTs; InaG-Sup UTRN- TGCGAACAGCAAInaTs; InaGs; InaCs; dGs; dAs; dAs; dCs; dAs; dGs; dCs; dAs; dAs; 497734117 m08 TGG InaTs; InaGs; InaG-Sup UTRN- GCGAACAGCAATInaGs; InaCs; InaGs; dAs; dAs; dCs; dAs; dGs; dCs; dAs; dAs; dTs; 497735118 m08 GGC InaGs; InaGs; InaC-Sup UTRN- AGTTCTGGCCAGInaAs; InaGs; InaTs; dTs; dCs; dTs; dGs; dGs; dCs; dCs; dAs; dGs; 497736119 m08 TGA InaTs; InaGs; InaA-Sup UTRN- AGAAGTGTTATTInaAs; InaGs; InaAs; dAs; dGs; dTs; dGs; dTs; dTs; dAs; dTs; dTs; 497737120 m08 GGA InaGs; InaGs; InaA-Sup UTRN- GAAGTGTTATTGInaGs; InaAs; InaAs; dGs; dTs; dGs; dTs; dTs; dAs; dTs; dTs; dGs; 497738121 m08 GAC InaGs; InaAs; InaC-Sup UTRN- GGTAGACTTGCGInaGs; InaGs; InaTs; dAs; dGs; dAs; dCs; dTs; dTs; dGs; dCs; dGs; 497739122 m08 CTA InaCs; InaTs; InaA-Sup UTRN- TAGACTTGCGCTAInaTs; InaAs; InaGs; dAs; dCs; dTs; dTs; dGs; dCs; dGs; dCs; dTs; 497740123 m08 CA InaAs; InaCs; InaA-Sup UTRN- AGACTTGCGCTAInaAs; InaGs; InaAs; dCs; dTs; dTs; dGs; dCs; dGs; dCs; dTs; dAs; 497741124 m08 CAT InaCs; InaAs; InaT-Sup UTRN- GACTTGCGCTACInaGs; InaAs; InaCs; dTs; dTs; dGs; dCs; dGs; dCs; dTs; dAs; dCs; 497742125 m08 ATT InaAs; InaTs; InaT-Sup UTRN- ACTTGCGCTACATInaAs; InaCs; InaTs; dTs; dGs; dCs; dGs; dCs; dTs; dAs; dCs; dAs; 497743126 m08 TA InaTs; InaTs; InaA-Sup UTRN- CTTGCGCTACATTInaCs; InaTs; InaTs; dGs; dCs; dGs; dCs; dTs; dAs; dCs; dAs; dTs; 497744127 m08 AA InaTs; InaAs; InaA-Sup UTRN- TTGCGCTACATTAInaTs; InaTs; InaGs; dCs; dGs; dCs; dTs; dAs; dCs; dAs; dTs; dTs; 497745128 m08 AT InaAs; InaAs; InaT-Sup UTRN- TGCGCTACATTAAInaTs; InaGs; InaCs; dGs; dCs; dTs; dAs; dCs; dAs; dTs; dTs; dAs; 497746129 m08 TA InaAs; InaTs; InaA-Sup UTRN- GCGCTACATTAATInaGs; InaCs; InaGs; dCs; dTs; dAs; dCs; dAs; dTs; dTs; dAs; dAs; 497747130 m08 AT InaTs; InaAs; InaT-Sup UTRN- GAAAGAACAGAGInaGs; InaAs; InaAs; dAs; dGs; dAs; dAs; dCs; dAs; dGs; dAs; dGs; 497748 131 m08 TGA InaTs; InaGs; InaA-Sup UTRN- AAAGAACAGAGTInaAs; InaAs; InaAs; dGs; dAs; dAs; dCs; dAs; dGs; dAs; dGs; dTs; 497749132 m08 GAC InaGs; InaAs; InaC-Sup UTRN- TCCATTCTGGTTCInaTs; InaCs; InaCs; dAs; dTs; dTs; dCs; dTs; dGs; dGs; dTs; dTs; 497750133 m08 GG InaCs; InaGs; InaG-Sup UTRN- CCATTCTGGTTCGInaCs; InaCs; InaAs; dTs; dTs; dCs; dTs; dGs; dGs; dTs; dTs; dCs; 497751134 m08 GT InaGs; InaGs; InaT-Sup UTRN- ATTCTGGTTCGGTInaAs; InaTs; InaTs; dCs; dTs; dGs; dGs; dTs; dTs; dCs; dGs; dGs; 497752135 m08 CT InaTs; InaCs; InaT-Sup UTRN- TTCTGGTTCGGTCInaTs; InaTs; InaCs; dTs; dGs; dGs; dTs; dTs; dCs; dGs; dGs; dTs; 497753136 m08 TC InaCs; InaTs; InaC-Sup UTRN- CCCCGATCTATTCInaCs; omeCs; InaCs; omeCs; InaGs; omeAs; InaTs; omeCs; 497729 112 m01TC InaTs; omeAs; InaTs; omeUs; InaCs; omeUs; InaC-Sup UTRN-CCCGATCTATTCT InaCs; omeCs; InaCs; omeGs; InaAs; omeUs; InaCs; omeUs;497730 113 m01 CC InaAs; omeUs; InaTs; omeCs; InaTs; omeCs; InaC-SupUTRN- CCGATCTATTCTCInaCs; omeCs; InaGs; omeAs; InaTs; omeCs; InaTs; omeAs; 497731 114 m01CA InaTs; omeUs; InaCs; omeUs; InaCs; omeCs; InaA-Sup UTRN- GCGCGATGCTGAInaGs; omeCs; InaGs; omeCs; InaGs; omeAs; InaTs; omeGs; 497732 115 m01ACT InaCs; omeUs; InaGs; omeAs; InaAs; omeCs; InaT-Sup UTRN-CTGCGAACAGCA InaCs; omeUs; InaGs; omeCs; InaGs; omeAs; InaAs; omeCs;497733 116 m01 ATG InaAs; omeGs; InaCs; omeAs; InaAs; omeUs; InaG-SupUTRN- TGCGAACAGCAAInaTs; omeGs; InaCs; omeGs; InaAs; omeAs; InaCs; omeAs; 497734 117 m01TGG InaGs; omeCs; InaAs; omeAs; InaTs; omeGs; InaG-Sup UTRN-GCGAACAGCAAT InaGs; omeCs; InaGs; omeAs; InaAs; omeCs; InaAs; omeGs;497735 118 m01 GGC InaCs; omeAs; InaAs; omeUs; InaGs; omeGs; InaC-SupUTRN- AGTTCTGGCCAGInaAs; omeGs; InaTs; omeUs; InaCs; omeUs; InaGs; omeGs; 497736 119 m01TGA InaCs; omeCs; InaAs; omeGs; InaTs; omeGs; InaA-Sup UTRN-AGAAGTGTTATT InaAs; omeGs; InaAs; omeAs; InaGs; omeUs; InaGs; omeUs;497737 120 m01 GGA InaTs; omeAs; InaTs; omeUs; InaGs; omeGs; InaA-SupUTRN- GAAGTGTTATTGInaGs; omeAs; InaAs; omeGs; InaTs; omeGs; InaTs; omeUs; 497738 121 m01GAC InaAs; omeUs; InaTs; omeGs; InaGs; omeAs; InaC-Sup UTRN-GGTAGACTTGCG InaGs; omeGs; InaTs; omeAs; InaGs; omeAs; InaCs; omeUs;497739 122 m01 CTA InaTs; omeGs; InaCs; omeGs; InaCs; omeUs; InaA-SupUTRN- TAGACTTGCGCTAInaTs; omeAs; InaGs; omeAs; InaCs; omeUs; InaTs; omeGs; 497740 123 m01CA InaCs; omeGs; InaCs; omeUs; InaAs; omeCs; InaA-Sup UTRN- AGACTTGCGCTAInaAs; omeGs; InaAs; omeCs; InaTs; omeUs; InaGs; omeCs; 497741 124 m01CAT InaGs; omeCs; InaTs; omeAs; InaCs; omeAs; InaT-Sup UTRN-GACTTGCGCTAC InaGs; omeAs; InaCs; omeUs; InaTs; omeGs; InaCs; omeGs;497742 125 m01 ATT InaCs; omeUs; InaAs; omeCs; InaAs; omeUs; InaT-SupUTRN- ACTTGCGCTACATInaAs; omeCs; InaTs; omeUs; InaGs; omeCs; InaGs; omeCs; 497743 126 m01TA InaTs; omeAs; InaCs; omeAs; InaTs; omeUs; InaA-Sup UTRN-CTTGCGCTACATT InaCs; omeUs; InaTs; omeGs; InaCs; omeGs; InaCs; omeUs;497744 127 m01 AA InaAs; omeCs; InaAs; omeUs; InaTs; omeAs; InaA-SupUTRN- TTGCGCTACATTAInaTs; omeUs; InaGs; omeCs; InaGs; omeCs; InaTs; omeAs; 497745 128 m01AT InaCs; omeAs; InaTs; omeUs; InaAs; omeAs; InaT-Sup UTRN-TGCGCTACATTAA InaTs; omeGs; InaCs; omeGs; InaCs; omeUs; InaAs; omeCs;497746 129 m01 TA InaAs; omeUs; InaTs; omeAs; InaAs; omeUs; InaA-SupUTRN- GCGCTACATTAATInaGs; omeCs; InaGs; omeCs; InaTs; omeAs; InaCs; omeAs; 497747 130 m01AT InaTs; omeUs; InaAs; omeAs; InaTs; omeAs; InaT-Sup UTRN- GAAAGAACAGAGInaGs; omeAs; InaAs; omeAs; InaGs; omeAs; InaAs; omeCs; 497748 131 m01TGA InaAs; omeGs; InaAs; omeGs; InaTs; omeGs; InaA-Sup UTRN-AAAGAACAGAGT InaAs; omeAs; InaAs; omeGs; InaAs; omeAs; InaCs; omeAs;497749 132 m01 GAC InaGs; omeAs; InaGs; omeUs; InaGs; omeAs; InaC-SupUTRN- TCCATTCTGGTTCInaTs; omeCs; InaCs; omeAs; InaTs; omeUs; InaCs; omeUs; 497750 133 m01GG InaGs; omeGs; InaTs; omeUs; InaCs; omeGs; InaG-Sup UTRN-CCATTCTGGTTCG InaCs; omeCs; InaAs; omeUs; InaTs; omeCs; InaTs; omeGs;497751 134 m01 GT InaGs; omeUs; InaTs; omeCs; InaGs; omeGs; InaT-SupUTRN- ATTCTGGTTCGGTInaAs; omeUs; InaTs; omeCs; InaTs; omeGs; InaGs; omeUs; 497752 135 m01CT InaTs; omeCs; InaGs; omeGs; InaTs; omeCs; InaT-Sup UTRN-TTCTGGTTCGGTC InaTs; omeUs; InaCs; omeUs; InaGs; omeGs; InaTs; omeUs;497753 136 m01 TC InaCs; omeGs; InaGs; omeUs; InaCs; omeUs; InaC-SupUTRN- CAGTATTATCTACInaCs; InaAs; InaGs; dTs; dAs; dTs; dTs; dAs; dTs; dCs; dTs; dAs; 320709157 m08 AC InaCs; InaAs; InaC-Sup UTRN- AGTATTATCTACAInaAs; InaGs; InaTs; dAs; dTs; dTs; dAs; dTs; dCs; dTs; dAs; dCs; 320710158 m08 CT InaAs; InaCs; InaT-Sup UTRN- TATCTACACTGATInaTs; InaAs; InaTs; dCs; dTs; dAs; dCs; dAs; dCs; dTs; dGs; dAs; 320715159 m08 CT InaTs; InaCs; InaT-Sup UTRN- ATCTACACTGATCInaAs; InaTs; InaCs; dTs; dAs; dCs; dAs; dCs; dTs; dGs; dAs; dTs; 320716160 m08 TT InaCs; InaTs; InaT-Sup UTRN- TGCACACTTGGATInaTs; InaGs; InaCs; dAs; dCs; dAs; dCs; dTs; dTs; dGs; dGs; dAs; 320742161 m08 TC InaTs; InaTs; InaC-Sup UTRN- GCACACTTGGATTInaGs; InaCs; InaAs; dCs; dAs; dCs; dTs; dTs; dGs; dGs; dAs; dTs; 320743162 m08 CT InaTs; InaCs; InaT-Sup UTRN- GGATTCTAACCTGInaGs; InaGs; InaAs; dTs; dTs; dCs; dTs; dAs; dAs; dCs; dCs; dTs; 320751163 m08 CA InaGs; InaCs; InaA-Sup UTRN- GATTCTAACCTGCInaGs; InaAs; InaTs; dTs; dCs; dTs; dAs; dAs; dCs; dCs; dTs; dGs; 320752164 m08 AA InaCs; InaAs; InaA-Sup UTRN- TTCTAACCTGCAAInaTs; InaTs; InaCs; dTs; dAs; dAs; dCs; dCs; dTs; dGs; dCs; dAs; 320754165 m08 TA InaAs; InaTs; InaA-Sup UTRN- TCTAACCTGCAATInaTs; InaCs; InaTs; dAs; dAs; dCs; dCs; dTs; dGs; dCs; dAs; dAs; 320755166 m08 AT InaTs; InaAs; InaT-Sup UTRN- ATTTTTATCTCTAInaAs; InaTs; InaTs; dTs; dTs; dTs; dAs; dTs; dCs; dTs; dCs; dTs; 320821167 m08 AA InaAs; InaAs; InaA-Sup UTRN- GAGTTAGATATCInaGs; InaAs; InaGs; dTs; dTs; dAs; dGs; dAs; dTs; dAs; dTs; dCs; 320838168 m08 AAG InaAs; InaAs; InaG-Sup UTRN- AGTTAGATATCAInaAs; InaGs; InaTs; dTs; dAs; dGs; dAs; dTs; dAs; dTs; dCs; dAs; 320839169 m08 AGG InaAs; InaGs; InaG-Sup UTRN- CATGGTATTAGATInaCs; InaAs; InaTs; dGs; dGs; dTs; dAs; dTs; dTs; dAs; dGs; dAs; 320858170 m08 TA InaTs; InaTs; InaA-Sup UTRN- GGTATTAGATTACInaGs; InaGs; InaTs; dAs; dTs; dTs; dAs; dGs; dAs; dTs; dTs; dAs; 320861171 m08 AC InaCs; InaAs; InaC-Sup UTRN- GTATTAGATTACAInaGs; InaTs; InaAs; dTs; dTs; dAs; dGs; dAs; dTs; dTs; dAs; dCs; 320862172 m08 CA InaAs; InaCs; InaA-Sup UTRN- TATTAGATTACACInaTs; InaAs; InaTs; dTs; dAs; dGs; dAs; dTs; dTs; dAs; dCs; dAs; 320863173 m08 AA InaCs; InaAs; InaA-Sup UTRN- TAGATTACACAATInaTs; InaAs; InaGs; dAs; dTs; dTs; dAs; dCs; dAs; dCs; dAs; dAs; 320866174 m08 AT InaTs; InaAs; InaT-Sup UTRN- ATCTTATTAGTACInaAs; InaTs; InaCs; dTs; dTs; dAs; dTs; dTs; dAs; dGs; dTs; dAs; 320918175 m08 TC InaCs; InaTs; InaC-Sup UTRN- ATTAGTACTCTTCInaAs; InaTs; InaTs; dAs; dGs; dTs; dAs; dCs; dTs; dCs; dTs; dTs; 320923176 m08 TG InaCs; InaTs; InaG-Sup UTRN- TTAGTACTCTTCTInaTs; InaTs; InaAs; dGs; dTs; dAs; dCs; dTs; dCs; dTs; dTs; dCs; 320924177 m08 GT InaTs; InaGs; InaT-Sup UTRN- AGTACTCTTCTGTInaAs; InaGs; InaTs; dAs; dCs; dTs; dCs; dTs; dTs; dCs; dTs; dGs; 320926178 m08 AG InaTs; InaAs; InaG-Sup UTRN- GGAATGGTTCAGInaGs; InaGs; InaAs; dAs; dTs; dGs; dGs; dTs; dTs; dCs; dAs; dGs; 320952179 m08 ACA InaAs; InaCs; InaA-Sup UTRN- GAATGGTTCAGAInaGs; InaAs; InaAs; dTs; dGs; dGs; dTs; dTs; dCs; dAs; dGs; dAs; 320953180 m08 CAG InaCs; InaAs; InaG-Sup UTRN- AATGGTTCAGACInaAs; InaAs; InaTs; dGs; dGs; dTs; dTs; dCs; dAs; dGs; dAs; dCs; 320954181 m08 AGT InaAs; InaGs; InaT-Sup UTRN- GGTTCAGACAGTInaGs; InaGs; InaTs; dTs; dCs; dAs; dGs; dAs; dCs; dAs; dGs; dTs; 320957182 m08 ATC InaAs; InaTs; InaC-Sup UTRN- TGTGGGTGTAAGInaTs; InaGs; InaTs; dGs; dGs; dGs; dTs; dGs; dTs; dAs; dAs; dGs; 320978183 m08 CAT InaCs; InaAs; InaT-Sup UTRN- GTGGGTGTAAGCInaGs; InaTs; InaGs; dGs; dGs; dTs; dGs; dTs; dAs; dAs; dGs; dCs; 320979184 m08 ATG InaAs; InaTs; InaG-Sup UTRN- GTAAGCATGGCCInaGs; InaTs; InaAs; dAs; dGs; dCs; dAs; dTs; dGs; dGs; dCs; dCs; 320985185 m08 ACC InaAs; InaCs; InaC-Sup UTRN- CTGCTCTGTGCCTInaCs; InaTs; InaGs; dCs; dTs; dCs; dTs; dGs; dTs; dGs; dCs; dCs; 321033186 m08 GA InaTs; InaGs; InaA-Sup UTRN- TGCTCTGTGCCTGInaTs; InaGs; InaCs; dTs; dCs; dTs; dGs; dTs; dGs; dCs; dCs; dTs; 321034187 m08 AG InaGs; InaAs; InaG-Sup UTRN- CTGAGTAAAGTAInaCs; InaTs; InaGs; dAs; dGs; dTs; dAs; dAs; dAs; dGs; dTs; dAs; 321044188 m08 GAG InaGs; InaAs; InaG-Sup UTRN- GTCTTCCCATAACInaGs; InaTs; InaCs; dTs; dTs; dCs; dCs; dCs; dAs; dTs; dAs; dAs; 497754189 m08 AG InaCs; InaAs; InaG-Sup UTRN- CCCATAACAGACInaCs; InaCs; InaCs; dAs; dTs; dAs; dAs; dCs; dAs; dGs; dAs; dCs; 497755190 m08 CTT InaCs; InaTs; InaT-Sup UTRN- CCATAACAGACCTInaCs; InaCs; InaAs; dTs; dAs; dAs; dCs; dAs; dGs; dAs; dCs; dCs; 497756191 m08 TC InaTs; InaTs; InaC-Sup UTRN- CCGCCACTGTCTCInaCs; InaCs; InaGs; dCs; dCs; dAs; dCs; dTs; dGs; dTs; dCs; dTs; 497757240 m08 GG InaCs; InaGs; InaG-Sup UTRN- TTTTCGCCGCCACInaTs; InaTs; InaTs; dTs; dCs; dGs; dCs; dCs; dGs; dCs; dCs; dAs; 497758241 m08 TG InaCs; InaTs; InaG-Sup UTRN- GTTTTCGCCGCCAInaGs; InaTs; InaTs; dTs; dTs; dCs; dGs; dCs; dCs; dGs; dCs; dCs; 497759242 m08 CT InaAs; InaCs; InaT-Sup UTRN- AGTTTTCGCCGCCInaAs; InaGs; InaTs; dTs; dTs; dTs; dCs; dGs; dCs; dCs; dGs; dCs; 497760243 m08 AC InaCs; InaAs; InaC-Sup UTRN- GAGTTTTCGCCGCInaGs; InaAs; InaGs; dTs; dTs; dTs; dTs; dCs; dGs; dCs; dCs; dGs; 497761244 m08 CA InaCs; InaCs; InaA-Sup UTRN- AGAGTTTTCGCCInaAs; InaGs; InaAs; dGs; dTs; dTs; dTs; dTs; dCs; dGs; dCs; dCs; 497762245 m08 GCC InaGs; InaCs; InaC-Sup UTRN- GAGAGTTTTCGCInaGs; InaAs; InaGs; dAs; dGs; dTs; dTs; dTs; dTs; dCs; dGs; dCs; 497763246 m08 CGC InaCs; InaGs; InaC-Sup UTRN- CAGAGAGTTTTCInaCs; InaAs; InaGs; dAs; dGs; dAs; dGs; dTs; dTs; dTs; dTs; dCs; 497764247 m08 GCC InaGs; InaCs; InaC-Sup UTRN- CCGCTTACAAGGInaCs; InaCs; InaGs; dCs; dTs; dTs; dAs; dCs; dAs; dAs; dGs; dGs; 497765248 m08 CAT InaCs; InaAs; InaT-Sup UTRN- GCTCCGCTTACAAInaGs; InaCs; InaTs; dCs; dCs; dGs; dCs; dTs; dTs; dAs; dCs; dAs; 497766249 m08 GG InaAs; InaGs; InaG-Sup UTRN- TGCTCCGCTTACAInaTs; InaGs; InaCs; dTs; dCs; dCs; dGs; dCs; dTs; dTs; dAs; dCs; 497767250 m08 AG InaAs; InaAs; InaG-Sup UTRN- TTTTGCTCCGCTTInaTs; InaTs; InaTs; dTs; dGs; dCs; dTs; dCs; dCs; dGs; dCs; dTs; 497768251 m08 AC InaTs; InaAs; InaC-Sup UTRN- ACGTTGAACCTTGInaAs; InaCs; InaGs; dTs; dTs; dGs; dAs; dAs; dCs; dCs; dTs; dTs; 497769252 m08 TT InaGs; InaTs; InaT-Sup UTRN- GACGTTGAACCTTInaGs; InaAs; InaCs; dGs; dTs; dTs; dGs; dAs; dAs; dCs; dCs; dTs; 497770253 m08 GT InaTs; InaGs; InaT-Sup UTRN- AGACGTTGAACCInaAs; InaGs; InaAs; dCs; dGs; dTs; dTs; dGs; dAs; dAs; dCs; dCs; 497771254 m08 TTG InaTs; InaTs; InaG-Sup UTRN- CAGACGTTGAACInaCs; InaAs; InaGs; dAs; dCs; dGs; dTs; dTs; dGs; dAs; dAs; dCs; 497772255 m08 CTT InaCs; InaTs; InaT-Sup UTRN- GCAGACGTTGAAInaGs; InaCs; InaAs; dGs; dAs; dCs; dGs; dTs; dTs; dGs; dAs; dAs; 497773256 m08 CCT InaCs; InaCs; InaT-Sup UTRN- AATGTCCAAGGCInaAs; InaAs; InaTs; dGs; dTs; dCs; dCs; dAs; dAs; dGs; dGs; dCs; 497774257 m08 GTG InaGs; InaTs; InaG-Sup UTRN- GTCGGAATTCTAInaGs; InaTs; InaCs; dGs; dGs; dAs; dAs; dTs; dTs; dCs; dTs; dAs; 497775258 m08 ATG InaAs; InaTs; InaG-Sup UTRN- AGTCGGAATTCTInaAs; InaGs; InaTs; dCs; dGs; dGs; dAs; dAs; dTs; dTs; dCs; dTs; 497776259 m08 AAT InaAs; InaAs; InaT-Sup UTRN- AAGTCGGAATTCInaAs; InaAs; InaGs; dTs; dCs; dGs; dGs; dAs; dAs; dTs; dTs; dCs; 497777260 m08 TAA InaTs; InaAs; InaA-Sup UTRN- GAAGTCGGAATTInaGs; InaAs; InaAs; dGs; dTs; dCs; dGs; dGs; dAs; dAs; dTs; dTs; 497778261 m08 CTA InaCs; InaTs; InaA-Sup UTRN- AGAAGTCGGAATInaAs; InaGs; InaAs; dAs; dGs; dTs; dCs; dGs; dGs; dAs; dAs; dTs; 497779262 m08 TCT InaTs; InaCs; InaT-Sup UTRN- CGTTGCGCTTCTCInaCs; InaGs; InaTs; dTs; dGs; dCs; dGs; dCs; dTs; dTs; dCs; dTs; 497780263 m08 CC InaCs; InaCs; InaC-Sup UTRN- GCGTTGCGCTTCTInaGs; InaCs; InaGs; dTs; dTs; dGs; dCs; dGs; dCs; dTs; dTs; dCs; 497781264 m08 CC InaTs; InaCs; InaC-Sup UTRN- AGCGTTGCGCTTCInaAs; InaGs; InaCs; dGs; dTs; dTs; dGs; dCs; dGs; dCs; dTs; dTs; 497782265 m08 TC InaCs; InaTs; InaC-Sup UTRN- GAGCGTTGCGCTInaGs; InaAs; InaGs; dCs; dGs; dTs; dTs; dGs; dCs; dGs; dCs; dTs; 497783266 m08 TCT InaTs; InaCs; InaT-Sup UTRN- TGAGCGTTGCGCInaTs; InaGs; InaAs; dGs; dCs; dGs; dTs; dTs; dGs; dCs; dGs; dCs; 497784267 m08 TTC InaTs; InaTs; InaC-Sup UTRN- GCGTGTGAGCGTInaGs; InaCs; InaGs; dTs; dGs; dTs; dGs; dAs; dGs; dCs; dGs; dTs; 497785268 m08 TGC InaTs; InaGs; InaC-Sup UTRN- TGCGTGTGAGCGInaTs; InaGs; InaCs; dGs; dTs; dGs; dTs; dGs; dAs; dGs; dCs; dGs; 497786269 m08 TTG InaTs; InaTs; InaG-Sup UTRN- GCGGTCTCTTGGTInaGs; InaCs; InaGs; dGs; dTs; dCs; dTs; dCs; dTs; dTs; dGs; dGs; 497787270 m08 GG InaTs; InaGs; InaG-Sup UTRN- CGCGGTCTCTTGInaCs; InaGs; InaCs; dGs; dGs; dTs; dCs; dTs; dCs; dTs; dTs; dGs; 497788271 m08 GTG InaGs; InaTs; InaG-Sup UTRN- CTGCGCGGTCTCTInaCs; InaTs; InaGs; dCs; dGs; dCs; dGs; dGs; dTs; dCs; dTs; dCs; 497789272 m08 TG InaTs; InaTs; InaG-Sup UTRN- ATATTCGCTATGTInaAs; InaTs; InaAs; dTs; dTs; dCs; dGs; dCs; dTs; dAs; dTs; dGs; 497790273 m08 TT InaTs; InaTs; InaT-Sup UTRN- TTCAATATATTCGInaTs; InaTs; InaCs; dAs; dAs; dTs; dAs; dTs; dAs; dTs; dTs; dCs; 497791274 m08 CT InaGs; InaCs; InaT-Sup UTRN- TTAACGATTCAAAInaTs; InaTs; InaAs; dAs; dCs; dGs; dAs; dTs; dTs; dCs; dAs; dAs; 497792275 m08 TT InaAs; InaTs; InaT-Sup UTRN- AGTTAACGATTCAInaAs; InaGs; InaTs; dTs; dAs; dAs; dCs; dGs; dAs; dTs; dTs; dCs; 497793276 m08 AA InaAs; InaAs; InaA-Sup UTRN- AAGTTAACGATTCInaAs; InaAs; InaGs; dTs; dTs; dAs; dAs; dCs; dGs; dAs; dTs; dTs; 497794277 m08 AA InaCs; InaAs; InaA-Sup UTRN- ACTAAGTTAACGInaAs; InaCs; InaTs; dAs; dAs; dGs; dTs; dTs; dAs; dAs; dCs; dGs; 497795278 m08 ATT InaAs; InaTs; InaT-Sup UTRN- AACTAAGTTAACInaAs; InaAs; InaCs; dTs; dAs; dAs; dGs; dTs; dTs; dAs; dAs; dCs; 497796279 m08 GAT InaGs; InaAs; InaT-Sup UTRN- CACTGCGTAAATInaCs; InaAs; InaCs; dTs; dGs; dCs; dGs; dTs; dAs; dAs; dAs; dTs; 497797280 m08 ACA InaAs; InaCs; InaA-Sup UTRN- GTGTCACTGCGTInaGs; InaTs; InaGs; dTs; dCs; dAs; dCs; dTs; dGs; dCs; dGs; dTs; 497798281 m08 AAA InaAs; InaAs; InaA-Sup UTRN- GTCTCGTGCAAGInaGs; InaTs; InaCs; dTs; dCs; dGs; dTs; dGs; dCs; dAs; dAs; dGs; 497799282 m08 TTG InaTs; InaTs; InaG-Sup UTRN- ATAATGTCTCGTGInaAs; InaTs; InaAs; dAs; dTs; dGs; dTs; dCs; dTs; dCs; dGs; dTs; 497800283 m08 CA InaGs; InaCs; InaA-Sup UTRN- ACGCTACTTGTTCInaAs; InaCs; InaGs; dCs; dTs; dAs; dCs; dTs; dTs; dGs; dTs; dTs; 497801284 m08 AG InaCs; InaAs; InaG-Sup UTRN- AACGCTACTTGTTInaAs; InaAs; InaCs; dGs; dCs; dTs; dAs; dCs; dTs; dTs; dGs; dTs; 497802285 m08 CA InaTs; InaCs; InaA-Sup UTRN- GAACGCTACTTGTInaGs; InaAs; InaAs; dCs; dGs; dCs; dTs; dAs; dCs; dTs; dTs; dGs; 497803286 m08 TC InaTs; InaTs; InaC-Sup UTRN- AGAACGCTACTTInaAs; InaGs; InaAs; dAs; dCs; dGs; dCs; dTs; dAs; dCs; dTs; dTs; 497804287 m08 GTT InaGs; InaTs; InaT-Sup UTRN- AAGAACGCTACTInaAs; InaAs; InaGs; dAs; dAs; dCs; dGs; dCs; dTs; dAs; dCs; dTs; 497805288 m08 TGT InaTs; InaGs; InaT-Sup UTRN- CCAAGAACGCTAInaCs; InaCs; InaAs; dAs; dGs; dAs; dAs; dCs; dGs; dCs; dTs; dAs; 497806289 m08 CTT InaCs; InaTs; InaT-Sup unc-232 CTACGCGTCGACInaCs; dTs; InaAs; dCs; InaGs; dCs; InaGs; dTs; InaCs; dGs; InaAs;497808 m12 GGT dCs; InaGs; dGs; InaT-Sup unc-232 CTACGCGTCGACInaCs; omeUs; InaAs; omeCs; InaGs; omeCs; InaGs; omeUs; 497808 m01 GGTInaCs; omeGs; InaAs; omeCs; InaGs; omeGs; InaT-Sup unc-293 CCGATTCGCGCGInaCs; dCs; InaGs; dAs; InaTs; dTs; InaCs; dGs; InaCs; dGs; InaCs;497809 m12 TAA dGs; InaTs; dAs; InaA-Sup unc-293 CCGATTCGCGCGInaCs; omeCs; InaGs; omeAs; InaTs; omeUs; InaCs; omeGs; 497809 m01 TAAInaCs; omeGs; InaCs; omeGs; InaTs; omeAs; InaA-Sup

BRIEF DESCRIPTION OF SEQUENCE LISTING

SEQ ID Chrom Gene Chr. Start Chr. End Strand 1 chr6 UTRN 144600872145186170 + 2 chr6 UTRN 144600872 145186170 − 3 chr10 Utrn 1208998512593533 − 4 chr10 Utrn 12089985 12593533 + 5 chr6 UTRN 144610489144610535 + 6 chr6 UTRN 144612994 144613040 + 7 chr6 UTRN 144614120144614162 + 8 chr6 UTRN 144614968 144615021 + 9 chr6 UTRN 144618862144618901 + 10 chr6 UTRN 144621690 144621714 + 11 chr6 UTRN 144625028144625096 + 12 chr6 UTRN 144625129 144625174 + 13 chr6 UTRN 144625319144625379 + 14 chr6 UTRN 144628965 144629011 + 15 chr6 UTRN 144633818144633869 + 16 chr6 UTRN 144633933 144633968 + 17 chr6 UTRN 144658267144658302 + 18 chr6 UTRN 144685087 144685140 + 19 chr6 UTRN 144695039144695063 + 20 chr6 UTRN 144699670 144699699 + 21 chr6 UTRN 144704043144704398 + 22 chr6 UTRN 144706312 144706345 + 23 chr6 UTRN 144706654144706704 + 24 chr6 UTRN 144721683 144721738 + 25 chr6 UTRN 144722580144722627 + 26 chr6 UTRN 144724848 144724889 + 27 chr6 UTRN 144727897144727947 + 28 chr6 UTRN 144746408 144746448 + 29 chr6 UTRN 144749102144749152 + 30 chr6 UTRN 144749948 144750026 + 31 chr6 UTRN 144750728144750789 + 32 chr6 UTRN 144750789 144750853 + 33 chr6 UTRN 144757162144757214 + 34 chr6 UTRN 144757214 144757274 + 35 chr6 UTRN 144758752144758807 + 36 chr6 UTRN 144758807 144758864 + 37 chr6 UTRN 144761513144761579 + 38 chr6 UTRN 144765456 144765506 + 39 chr6 UTRN 144768420144768461 + 40 chr6 UTRN 144768737 144768764 + 41 chr6 UTRN 144772549144772627 + 42 chr6 UTRN 144774960 144775001 + 43 chr6 UTRN 144779914144779960 + 44 chr6 UTRN 144780026 144780070 + 45 chr6 UTRN 144780278144780324 + 46 chr6 UTRN 144783879 144783933 + 47 chr6 UTRN 144783933144783995 + 48 chr6 UTRN 144800953 144800999 + 49 chr6 UTRN 144802780144802822 + 50 chr6 UTRN 144803427 144803473 + 51 chr6 UTRN 144803714144803742 + 52 chr6 UTRN 144803774 144803849 + 53 chr6 UTRN 144806673144806714 + 54 chr6 UTRN 144808684 144808739 + 55 chr6 UTRN 144808739144808803 + 56 chr6 UTRN 144809834 144809881 + 57 chr6 UTRN 144811266144811310 + 58 chr6 UTRN 144814476 144814522 + 59 chr6 UTRN 144815156144815199 + 60 chr6 UTRN 144820469 144820529 + 61 chr6 UTRN 144832193144832243 + 62 chr6 UTRN 144835120 144835166 + 63 chr6 UTRN 144835862144835907 + 64 chr6 UTRN 144837423 144837465 + 65 chr6 UTRN 144837943144837989 + 66 chr6 UTRN 144844263 144844304 + 67 chr6 UTRN 144858722144858798 + 68 chr6 UTRN 144870778 144870817 + 69 chr6 UTRN 144871113144871154 + 70 chr6 UTRN 144872123 144872165 + 71 chr6 UTRN 144872599144872669 + 72 chr6 UTRN 144873625 144873662 + 73 chr6 UTRN 144875136144875182 + 74 chr6 UTRN 144875895 144875938 + 75 chr6 UTRN 144886315144886378 + 76 chr6 UTRN 144904604 144904645 + 77 chr6 UTRN 144905276144905300 + 78 chr6 UTRN 144906334 144906358 + 79 chr6 UTRN 144907025144907055 + 80 chr6 UTRN 144908864 144908908 + 81 chr6 UTRN 144909055144909078 + 82 chr6 UTRN 144910040 144910085 + 83 chr6 UTRN 144918990144919013 + 84 chr6 UTRN 144935390 144935427 + 85 chr6 UTRN 144938199144938248 + 86 chr6 UTRN 144941446 144941489 + 87 chr6 UTRN 144941551144941596 + 88 chr6 UTRN 144941700 144941748 + 89 chr6 UTRN 144941856144941912 + 90 chr6 UTRN 144941912 144941988 + 91 chr6 UTRN 144942080144942136 + 92 chr6 UTRN 144944667 144944712 + 93 chr6 UTRN 144945160144945207 + 94 chr6 UTRN 144950918 144950987 + 95 chr6 UTRN 144952595144952650 + 96 chr6 UTRN 144954758 144954804 + 97 chr6 UTRN 144960952144960996 + 98 chr6 UTRN 144968386 144968438 + 99 chr6 UTRN 144981668144981709 + 100 chr6 UTRN 144985026 144985072 + 101 chr6 UTRN 144999637144999686 + 102 chr6 UTRN 144999750 144999785 + 103 chr6 UTRN 144999904144999956 + 104 chr6 UTRN 145012224 145012561 + 105 chr6 UTRN 145017897145017969 + 106 chr6 UTRN 145017978 145018021 + 107 chr6 UTRN 145019229145019261 + 108 chr6 UTRN 145021232 145021278 + 109 chr6 UTRN 145021336145021382 + 110 chr6 UTRN 145031285 145031331 + 111 chr6 UTRN 145038424145038467 + 112 chr6 UTRN 145042706 145042751 + 113 chr6 UTRN 145047775145047820 + 114 chr6 UTRN 145051549 145051592 + 115 chr6 UTRN 145061899145061941 + 116 chr6 UTRN 145063569 145063615 + 117 chr6 UTRN 145069445145069497 + 118 chr6 UTRN 145072959 145073005 + 119 chr6 UTRN 145079115145079162 + 120 chr6 UTRN 145079204 145079271 + 121 chr6 UTRN 145080780145080816 + 122 chr6 UTRN 145080843 145080885 + 123 chr6 UTRN 145081884145081930 + 124 chr6 UTRN 145087734 145087827 + 125 chr6 UTRN 145087827145087911 + 126 chr6 UTRN 145088046 145088124 + 127 chr6 UTRN 145088210145088245 + 128 chr6 UTRN 145088678 145088723 + 129 chr6 UTRN 145090281145090327 + 130 chr6 UTRN 145090884 145090934 + 131 chr6 UTRN 145093542145093591 + 132 chr6 UTRN 145094155 145094199 + 133 chr6 UTRN 145096714145096756 + 134 chr6 UTRN 145101237 145101284 + 135 chr6 UTRN 145101598145101642 + 136 chr6 UTRN 145127145 145127194 + 137 chr6 UTRN 145127467145127507 + 138 chr6 UTRN 145127866 145127929 + 139 chr6 UTRN 145128105145128160 + 140 chr6 UTRN 145128415 145128460 + 141 chr6 UTRN 145132350145132397 + 142 chr6 UTRN 145132917 145132974 + 143 chr6 UTRN 145133779145133802 + 144 chr6 UTRN 145134097 145134169 + 145 chr6 UTRN 145134835145134881 + 146 chr6 UTRN 145142034 145142135 + 147 chr6 UTRN 145142629145142676 + 148 chr6 UTRN 145148750 145148806 + 149 chr6 UTRN 145149936145149984 + 150 chr6 UTRN 145153900 145154300 + 151 chr6 UTRN 145154735145154782 + 152 chr6 UTRN 145155438 145155468 + 153 chr6 UTRN 145156972145157019 + 154 chr6 UTRN 145157440 145157555 + 155 chr6 UTRN 145157566145157621 + 156 chr6 UTRN 145158149 145158194 + 157 chr6 UTRN 145160356145160409 + 158 chr6 UTRN 145161881 145161927 + 159 chr6 UTRN 145167107145167151 + 160 chr6 UTRN 145167205 145167243 + 161 chr6 UTRN 145168292145168344 + 162 chr6 UTRN 145169033 145169085 + 163 chr6 UTRN 145169156145169202 + 164 chr6 UTRN 145169270 145169315 + 165 chr6 UTRN 145171814145171863 + 166 chr6 UTRN 145173631 145173718 + 167 chr6 UTRN 144608489144612535 + 168 chr6 UTRN 144610994 144615040 + 169 chr6 UTRN 144612120144616162 + 170 chr6 UTRN 144612968 144617021 + 171 chr6 UTRN 144616862144620901 + 172 chr6 UTRN 144619690 144623714 + 173 chr6 UTRN 144623028144627096 + 174 chr6 UTRN 144623129 144627174 + 175 chr6 UTRN 144623319144627379 + 176 chr6 UTRN 144626965 144631011 + 177 chr6 UTRN 144631818144635869 + 178 chr6 UTRN 144631933 144635968 + 179 chr6 UTRN 144656267144660302 + 180 chr6 UTRN 144683087 144687140 + 181 chr6 UTRN 144693039144697063 + 182 chr6 UTRN 144697670 144701699 + 183 chr6 UTRN 144702043144706398 + 184 chr6 UTRN 144704312 144708345 + 185 chr6 UTRN 144704654144708704 + 186 chr6 UTRN 144719683 144723738 + 187 chr6 UTRN 144720580144724627 + 188 chr6 UTRN 144722848 144726889 + 189 chr6 UTRN 144725897144729947 + 190 chr6 UTRN 144744408 144748448 + 191 chr6 UTRN 144747102144751152 + 192 chr6 UTRN 144747948 144752026 + 193 chr6 UTRN 144748728144752789 + 194 chr6 UTRN 144748789 144752853 + 195 chr6 UTRN 144755162144759214 + 196 chr6 UTRN 144755214 144759274 + 197 chr6 UTRN 144756752144760807 + 198 chr6 UTRN 144756807 144760864 + 199 chr6 UTRN 144759513144763579 + 200 chr6 UTRN 144763456 144767506 + 201 chr6 UTRN 144766420144770461 + 202 chr6 UTRN 144766737 144770764 + 203 chr6 UTRN 144770549144774627 + 204 chr6 UTRN 144772960 144777001 + 205 chr6 UTRN 144777914144781960 + 206 chr6 UTRN 144778026 144782070 + 207 chr6 UTRN 144778278144782324 + 208 chr6 UTRN 144781879 144785933 + 209 chr6 UTRN 144781933144785995 + 210 chr6 UTRN 144798953 144802999 + 211 chr6 UTRN 144800780144804822 + 212 chr6 UTRN 144801427 144805473 + 213 chr6 UTRN 144801714144805742 + 214 chr6 UTRN 144801774 144805849 + 215 chr6 UTRN 144804673144808714 + 216 chr6 UTRN 144806684 144810739 + 217 chr6 UTRN 144806739144810803 + 218 chr6 UTRN 144807834 144811881 + 219 chr6 UTRN 144809266144813310 + 220 chr6 UTRN 144812476 144816522 + 221 chr6 UTRN 144813156144817199 + 222 chr6 UTRN 144818469 144822529 + 223 chr6 UTRN 144830193144834243 + 224 chr6 UTRN 144833120 144837166 + 225 chr6 UTRN 144833862144837907 + 226 chr6 UTRN 144835423 144839465 + 227 chr6 UTRN 144835943144839989 + 228 chr6 UTRN 144842263 144846304 + 229 chr6 UTRN 144856722144860798 + 230 chr6 UTRN 144868778 144872817 + 231 chr6 UTRN 144869113144873154 + 232 chr6 UTRN 144870123 144874165 + 233 chr6 UTRN 144870599144874669 + 234 chr6 UTRN 144871625 144875662 + 235 chr6 UTRN 144873136144877182 + 236 chr6 UTRN 144873895 144877938 + 237 chr6 UTRN 144884315144888378 + 238 chr6 UTRN 144902604 144906645 + 239 chr6 UTRN 144903276144907300 + 240 chr6 UTRN 144904334 144908358 + 241 chr6 UTRN 144905025144909055 + 242 chr6 UTRN 144906864 144910908 + 243 chr6 UTRN 144907055144911078 + 244 chr6 UTRN 144908040 144912085 + 245 chr6 UTRN 144916990144921013 + 246 chr6 UTRN 144933390 144937427 + 247 chr6 UTRN 144936199144940248 + 248 chr6 UTRN 144939446 144943489 + 249 chr6 UTRN 144939551144943596 + 250 chr6 UTRN 144939700 144943748 + 251 chr6 UTRN 144939856144943912 + 252 chr6 UTRN 144939912 144943988 + 253 chr6 UTRN 144940080144944136 + 254 chr6 UTRN 144942667 144946712 + 255 chr6 UTRN 144943160144947207 + 256 chr6 UTRN 144948918 144952987 + 257 chr6 UTRN 144950595144954650 + 258 chr6 UTRN 144952758 144956804 + 259 chr6 UTRN 144958952144962996 + 260 chr6 UTRN 144966386 144970438 + 261 chr6 UTRN 144979668144983709 + 262 chr6 UTRN 144983026 144987072 + 263 chr6 UTRN 144997637145001686 + 264 chr6 UTRN 144997750 145001785 + 265 chr6 UTRN 144997904145001956 + 266 chr6 UTRN 145010224 145014561 + 267 chr6 UTRN 145015897145019969 + 268 chr6 UTRN 145015978 145020021 + 269 chr6 UTRN 145017229145021261 + 270 chr6 UTRN 145019232 145023278 + 271 chr6 UTRN 145019336145023382 + 272 chr6 UTRN 145029285 145033331 + 273 chr6 UTRN 145036424145040467 + 274 chr6 UTRN 145040706 145044751 + 275 chr6 UTRN 145045775145049820 + 276 chr6 UTRN 145049549 145053592 + 277 chr6 UTRN 145059899145063941 + 278 chr6 UTRN 145061569 145065615 + 279 chr6 UTRN 145067445145071497 + 280 chr6 UTRN 145070959 145075005 + 281 chr6 UTRN 145077115145081162 + 282 chr6 UTRN 145077204 145081271 + 283 chr6 UTRN 145078780145082816 + 284 chr6 UTRN 145078843 145082885 + 285 chr6 UTRN 145079884145083930 + 286 chr6 UTRN 145085734 145089827 + 287 chr6 UTRN 145085827145089911 + 288 chr6 UTRN 145086046 145090124 + 289 chr6 UTRN 145086210145090245 + 290 chr6 UTRN 145086678 145090723 + 291 chr6 UTRN 145088281145092327 + 292 chr6 UTRN 145088884 145092934 + 293 chr6 UTRN 145091542145095591 + 294 chr6 UTRN 145092155 145096199 + 295 chr6 UTRN 145094714145098756 + 296 chr6 UTRN 145099237 145103284 + 297 chr6 UTRN 145099598145103642 + 298 chr6 UTRN 145125145 145129194 + 299 chr6 UTRN 145125467145129507 + 300 chr6 UTRN 145125866 145129929 + 301 chr6 UTRN 145126105145130160 + 302 chr6 UTRN 145126415 145130460 + 303 chr6 UTRN 145130350145134397 + 304 chr6 UTRN 145130917 145134974 + 305 chr6 UTRN 145131779145135802 + 306 chr6 UTRN 145132097 145136169 + 307 chr6 UTRN 145132835145136881 + 308 chr6 UTRN 145140034 145144135 + 309 chr6 UTRN 145140629145144676 + 310 chr6 UTRN 145146750 145150806 + 311 chr6 UTRN 145147936145151984 + 312 chr6 UTRN 145151900 145156300 + 313 chr6 UTRN 145152735145156782 + 314 chr6 UTRN 145153438 145157468 + 315 chr6 UTRN 145154972145159019 + 316 chr6 UTRN 145155440 145159555 + 317 chr6 UTRN 145155566145159621 + 318 chr6 UTRN 145156149 145160194 + 319 chr6 UTRN 145158356145162409 + 320 chr6 UTRN 145159881 145163927 + 321 chr6 UTRN 145165107145169151 + 322 chr6 UTRN 145165205 145169243 + 323 chr6 UTRN 145166292145170344 + 324 chr6 UTRN 145167033 145171085 + 325 chr6 UTRN 145167156145171202 + 326 chr6 UTRN 145167270 145171315 + 327 chr6 UTRN 145169814145173863 + 328 chr6 UTRN 145171631 145175718 + 329 chr6 UTRN 144608031144608073 − 330 chr6 UTRN 144612926 144612972 − 331 chr6 UTRN 144628552144628595 − 332 chr6 UTRN 144633946 144633970 − 333 chr6 UTRN 144650739144650804 − 334 chr6 UTRN 144657045 144657093 − 335 chr6 UTRN 144696995144697041 − 336 chr6 UTRN 144747612 144747674 − 337 chr6 UTRN 144747879144747925 − 338 chr6 UTRN 144759816 144759863 − 339 chr6 UTRN 144768238144768312 − 340 chr6 UTRN 144780036 144780082 − 341 chr6 UTRN 144782886144782935 − 342 chr6 UTRN 144795766 144795789 − 343 chr6 UTRN 144806556144806601 − 344 chr6 UTRN 144854365 144854401 − 345 chr6 UTRN 144858769144858809 − 346 chr6 UTRN 144861763 144861805 − 347 chr6 UTRN 144865560144865594 − 348 chr6 UTRN 144871095 144871118 − 349 chr6 UTRN 144872146144872179 − 350 chr6 UTRN 144873792 144873815 − 351 chr6 UTRN 144875726144875775 − 352 chr6 UTRN 144881389 144881429 − 353 chr6 UTRN 144902992144903093 − 354 chr6 UTRN 144913242 144913292 − 355 chr6 UTRN 144916606144916629 − 356 chr6 UTRN 144953033 144953075 − 357 chr6 UTRN 144957938144957985 − 358 chr6 UTRN 144960849 144960900 − 359 chr6 UTRN 144963737144963802 − 360 chr6 UTRN 144980957 144981000 − 361 chr6 UTRN 144981226144981271 − 362 chr6 UTRN 144981350 144981396 − 363 chr6 UTRN 144981507144981542 − 364 chr6 UTRN 144983660 144983707 − 365 chr6 UTRN 145005066145005095 − 366 chr6 UTRN 145005500 145005548 − 367 chr6 UTRN 145021339145021384 − 368 chr6 UTRN 145036068 145036136 − 369 chr6 UTRN 145036766145036820 − 370 chr6 UTRN 145038552 145038606 − 371 chr6 UTRN 145058056145058096 − 372 chr6 UTRN 145059402 145059450 − 373 chr6 UTRN 145060834145060905 − 374 chr6 UTRN 145062448 145062475 − 375 chr6 UTRN 145063125145063160 − 376 chr6 UTRN 145063273 145063302 − 377 chr6 UTRN 145071318145071359 − 378 chr6 UTRN 145079495 145079543 − 379 chr6 UTRN 145090227145090266 − 380 chr6 UTRN 145095420 145095465 − 381 chr6 UTRN 145097191145097232 − 382 chr6 UTRN 145098097 145098128 − 383 chr6 UTRN 145098960145099005 − 384 chr6 UTRN 145106983 145107024 − 385 chr6 UTRN 145124174145124220 − 386 chr6 UTRN 145128278 145128325 − 387 chr6 UTRN 145142105145142152 − 388 chr6 UTRN 145149926 145149972 − 389 chr6 UTRN 145153110145153155 − 390 chr6 UTRN 145155586 145155641 − 391 chr6 UTRN 145156956145157020 − 392 chr6 UTRN 145161886 145161931 − 393 chr6 UTRN 145166490145166527 − 394 chr6 UTRN 145167701 145167736 − 395 chr6 UTRN 145173585145173627 − 396 chr6 UTRN 144606031 144610073 − 397 chr6 UTRN 144610926144614972 − 398 chr6 UTRN 144626552 144630595 − 399 chr6 UTRN 144631946144635970 − 400 chr6 UTRN 144648739 144652804 − 401 chr6 UTRN 144655045144659093 − 402 chr6 UTRN 144694995 144699041 − 403 chr6 UTRN 144745612144749674 − 404 chr6 UTRN 144745879 144749925 − 405 chr6 UTRN 144757816144761863 − 406 chr6 UTRN 144766238 144770312 − 407 chr6 UTRN 144778036144782082 − 408 chr6 UTRN 144780886 144784935 − 409 chr6 UTRN 144793766144797789 − 410 chr6 UTRN 144804556 144808601 − 411 chr6 UTRN 144852365144856401 − 412 chr6 UTRN 144856769 144860809 − 413 chr6 UTRN 144859763144863805 − 414 chr6 UTRN 144863560 144867594 − 415 chr6 UTRN 144869095144873118 − 416 chr6 UTRN 144870146 144874179 − 417 chr6 UTRN 144871792144875815 − 418 chr6 UTRN 144873726 144877775 − 419 chr6 UTRN 144879389144883429 − 420 chr6 UTRN 144900992 144905093 − 421 chr6 UTRN 144911242144915292 − 422 chr6 UTRN 144914606 144918629 − 423 chr6 UTRN 144951033144955075 − 424 chr6 UTRN 144955938 144959985 − 425 chr6 UTRN 144958849144962900 − 426 chr6 UTRN 144961737 144965802 − 427 chr6 UTRN 144978957144983000 − 428 chr6 UTRN 144979226 144983271 − 429 chr6 UTRN 144979350144983396 − 430 chr6 UTRN 144979507 144983542 − 431 chr6 UTRN 144981660144985707 − 432 chr6 UTRN 145003066 145007095 − 433 chr6 UTRN 145003500145007548 − 434 chr6 UTRN 145019339 145023384 − 435 chr6 UTRN 145034068145038136 − 436 chr6 UTRN 145034766 145038820 − 437 chr6 UTRN 145036552145040606 − 438 chr6 UTRN 145056056 145060096 − 439 chr6 UTRN 145057402145061450 − 440 chr6 UTRN 145058834 145062905 − 441 chr6 UTRN 145060448145064475 − 442 chr6 UTRN 145061125 145065160 − 443 chr6 UTRN 145061273145065302 − 444 chr6 UTRN 145069318 145073359 − 445 chr6 UTRN 145077495145081543 − 446 chr6 UTRN 145088227 145092266 − 447 chr6 UTRN 145093420145097465 − 448 chr6 UTRN 145095191 145099232 − 449 chr6 UTRN 145096097145100128 − 450 chr6 UTRN 145096960 145101005 − 451 chr6 UTRN 145104983145109024 − 452 chr6 UTRN 145122174 145126220 − 453 chr6 UTRN 145126278145130325 − 454 chr6 UTRN 145140105 145144152 − 455 chr6 UTRN 145147926145151972 − 456 chr6 UTRN 145151110 145155155 − 457 chr6 UTRN 145153586145157641 − 458 chr6 UTRN 145154956 145159020 − 459 chr6 UTRN 145159886145163931 − 460 chr6 UTRN 145164490 145168527 − 461 chr6 UTRN 145165701145169736 − 462 chr6 UTRN 145171585 145175627 −

Single Strand Oligonucleotides (Antisense Strand of Target Gene)

SegID range: 463-307980

SegIDs w/o G Runs:

475-1059, 1073-1276, 1291-1599, 1613-1879, 1893-1923, 1937-1959,1974-2113, 2122-2142, 2156-2229, 2243-2253, 2267-2357, 2371-2393,2419-2489, 2503-2619, 2631-2647, 2669-2671, 2685-2704, 2724-2790,2801-2816, 2828-2896, 2908-2928, 2942, 2956-3326, 3348-3504, 3519-3557,3572-3632, 3646-3692, 3707-3750, 3764-3800, 3808-3891, 3898-3902,3921-3950, 3964-3975, 3990-4004, 4018-4031, 4056-4189, 4203-4267,4281-4556, 4570-4943, 4957-5145, 5166-5311, 5327-5419, 5433-5543,5557-5635, 5649-6239, 6253-6380, 6394-6496, 6510-6928, 6942-7134,7157-8180, 8201-8459, 8481-8492, 8506-8696, 8710-8833, 8847-8869,8883-8932, 8946-8949, 8971-9192, 9226-9244, 9258-9288, 9303-9312,9339-9437, 9451-9462, 9476-9538, 9552-9616, 9630-9646, 9661-9667,9681-9971, 9985-10440, 10454-10469, 10483-10649, 10663-10752,10766-10918, 10933-11098, 11112-11278, 11292-11840, 11855-11982,11996-12019, 12033-12186, 12200-12341, 12355-12677, 12691-12843,12857-12865, 12879-12917, 12931-12972, 12985-13071, 13082-13115,13129-13176, 13191-13587, 13602-13770, 13792-13956, 13970-13976,13990-14287, 14297-14309, 14332-14445, 14458-14509, 14541-14573,14587-14641, 14664-14742, 14756-14774, 14788-14989, 14997-15207,15221-15266, 15281-15464, 15478-15530, 15544-15560, 15574-16579,16593-16792, 16806-16869, 16883-17116, 17130-17466, 17480-17536,17542-17564, 17579-17602, 17616-17638, 17648-17835, 17849-18046,18060-18216, 18229, 18243-18292, 18306-18372, 18386-18565, 18579-18588,18602-18655, 18669-19217, 19231-19331, 19343-19398, 19412-19446,19454-19613, 19627-19742, 19756-19759, 19775-20189, 20203-20233,20247-20448, 20467-20485, 20499-20519, 20534-20584, 20602-20743,20757-20796, 20811-20822, 20836-20882, 20900-20951, 20958-20989,21003-21011, 21025-21035, 21049-21105, 21133-21139, 21153-21170,21184-21188, 21214-21263, 21277-21301, 21316-21366, 21380-21395,21411-21523, 21537-21562, 21577-21581, 21599-21626, 21647-21658,21673-21738, 21752-21831, 21866-21901, 21916-21945, 21959-22101,22122-22128, 22143-22200, 22215-22250, 22264-22277, 22292-22327,22336-22432, 22446-22475, 22489-22514, 22528-22646, 22660-22692,22706-22779, 22793-22983, 22997-23069, 23083-23804, 23814-23837,23840-23852, 23859-24072, 24086-24248, 24262-24582, 24596-24663,24677-24696, 24710-24956, 24972-24982, 25008-25033, 25047-25061,25095-25108, 25122-25126, 25140-25158, 25172-25195, 25210-25260,25274-25359, 25373-25586, 25600-25610, 25624-25764, 25778-25793,25818-25820, 25840-25972, 25992-26034, 26048-26055, 26077-26104,26118-26444, 26458-26476, 26490-26515, 26547-26608, 26622-26642,26657-26681, 26695-26711, 26725-26862, 26876-26986, 27000-27115,27129-27154, 27168-27230, 27244-27629, 27643-27707, 27721-27815,27829-27876, 27890-27985, 27999-28050, 28063-28099, 28113-28114,28128-28204, 28218-28262, 28276-28358, 28397-28445, 28460-28502,28516-28662, 28676-28764, 28778-28795, 28809, 28822-28825, 28850-28895,28903-28929, 28943-29021, 29035-29116, 29130-29368, 29382-29690,29714-30031, 30045-30129, 30143-30521, 30539, 30553-30560, 30592-30600,30614-30756, 30770-31738, 31752-31761, 31775-31847, 31861-32143,32157-32493, 32507-32577, 32615-32736, 32750-32752, 32767-32787,32801-33022, 33036-33051, 33065-33173, 33188-33206, 33220-33275,33290-34111, 34120-34125, 34139-34540, 34554-34737, 34745-34749,34765-34832, 34846-34947, 34961-35017, 35031-35094, 35108-35281,35295-35380, 35394-35789, 35803-35833, 35848-36211, 36225-36465,36479-36492, 36497-36531, 36538-36578, 36591-36607, 36621-36634,36637-36676, 36696-36710, 36724-36759, 36772-36874, 36888-37002,37016-37457, 37471-37574, 37588-37760, 37776-37783, 37799-37807,37830-38163, 38177-38309, 38321-38401, 38415-38496, 38510-38566,38580-38734, 38748-38759, 38773-38778, 38792-38872, 38886-38956,38970-39034, 39048-39451, 39465, 39479-39663, 39677-40297, 40312-40520,40534-40733, 40747-40760, 40777-41542, 41561-41601, 41615-41628,41642-41649, 41663-41667, 41682-41697, 41711-41897, 41942-41944,41958-41980, 41994-42066, 42080-42228, 42242-42255, 42265-42267,42281-42287, 42296-42319, 42333-42384, 42398-42467, 42482-42519,42532-42659, 42673-43048, 43062-43311, 43325-43450, 43464-43552,43566-43662, 43673-43718, 43737-43750, 43753-43783, 43793-43813,43822-43838, 43852-43993, 44007-44063, 44077-44127, 44141-44202, 44216,44231-44802, 44816-44819, 44840-44959, 44973-45049, 45101-45190,45204-45535, 45549-45555, 45569-45934, 45955-46195, 46209-46479,46506-46603, 46630-46687, 46701-46727, 46741-46803, 46817-47031,47045-47105, 47119-47451, 47465-47571, 47585-47612, 47620-47750,47754-47758, 47780-47842, 47856-47937, 47951-48006, 48021-48043,48057-48156, 48170-48171, 48186-48564, 48578-48700, 48714-49138,49152-49252, 49266-49402, 49416-49800, 49814-50016, 50038-50172,50186-50318, 50331-50463, 50478-50632, 50646-50683, 50700-50743,50757-50958, 50972-51254, 51268-51609, 51624-51656, 51670-51769,51783-52236, 52250-52251, 52274-52606, 52621-52912, 52926-53012,53033-53457, 53471-54305, 54319-54322, 54336-54735, 54749-54831,54845-54932, 54946-55069, 55084-55468, 55483-55499, 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248794-249701, 249715-249754,249768-249795, 249809-250005, 250020-250280, 250294-250547,250561-250995, 251009-251010, 251024-251037, 251051-251173,251187-251259, 251279-251293, 251307-251447, 251469-251618,251642-251796, 251810-251954, 251968-251984, 251998-252011,252025-252164, 252178-252306, 252320-252395, 252409-252424,252438-252523, 252550-252715, 252729-252766, 252780-252842,252857-253206, 253220-253514, 253538-253596, 253603-253622,253635-253641, 253651-253662, 253667-253723, 253738-253965,253979-254047, 254064-254083, 254105-254131, 254136-254142, 254164,254173-254733, 254763-254770, 254786-255162, 255177-255204,255218-255316, 255330-255338, 255352-255587, 255601-255723,255737-255797, 255811-255860, 255874-255876, 255890-256359,256374-256464, 256478-256521, 256535-256755, 256769-256857,256871-257322, 257336-257598, 257612-257689, 257705-257706,257721-257884, 257903-257957, 257971-257983, 258003-258013,258039-258079, 258093-258097, 258111-258189, 258204-258250,258264-258385, 258406-258417, 258431-258468, 258482-258686,258700-259216, 259230-259282, 259297-260016, 260030-260085,260100-260187, 260201-260596, 260622-260650, 260664-260689,260712-261028, 261042-261279, 261293-262000, 262015-262087,262101-262221, 262235-262398, 262412-262413, 262428-263498,263512-263868, 263882-264020, 264034-264078, 264092-264118,264133-264206, 264220-264607, 264633-264635, 264649-264756,264770-265001, 265015-265037, 265051-265233, 265247-265339,265354-265386, 265400-265411, 265426-265477, 265491-265494,265508-265528, 265532-265546, 265560-265670, 265684-265895,265909-266004, 266018-266116, 266130-266197, 266211-266357,266371-266529, 266543-266570, 266584-266712, 266726-266914,266930-267051, 267065-267079, 267093-267102, 267116-267121,267135-267196, 267210-267285, 267299-267571, 267585-267853,267867-268072, 268086-268103, 268126-268169, 268183-268273,268287-268430, 268444-268873, 268887-269049, 269064-269149,269163-269255, 269269-269373, 269387-269555, 269569-269600,269614-269701, 269715-269946, 269961-270559, 270573-270614,270629-270935, 270949-271482, 271497-272342, 272356-272431,272445-272631, 272644-272657, 272671-272916, 272932-273063,273077-273264, 273280-273294, 273308-273388, 273403-273407,273421-273452, 273466-274132, 274146-274302, 274316-274599,274613-274649, 274663-274704, 274727-274886, 274900-274904,274918-274976, 274990-275062, 275076-275288, 275302-275464,275473-275681, 275696-275982, 275996-276122, 276136-276144,276158-276182, 276197-276392, 276406-276735, 276749-277133,277148-277481, 277495-277666, 277680-277980, 277994-278092,278106-278540, 278554-279095, 279109-279334, 279348-279830,279844-280186, 280201-280224, 280239-280571, 280587-280648,280663-280717, 280732-280785, 280800-280841, 280862-280902,280921-280972, 280986-281177, 281192-281212, 281226-281263,281277-281281, 281295-281947, 281961-282357, 282371-282513,282527-282652, 282667-282758, 282772-282830, 282844-282858,282872-282992, 283007-283056, 283070-283107, 283121-283484,283498-283683, 283697-283865, 283879-284069, 284083-284105,284119-284144, 284158-284162, 284176-284184, 284198-284299,284313-284402, 284416-284548, 284562-284675, 284692-284701,284715-284807, 284833-284993, 285007-285067, 285090-285303,285317-285610, 285624-285638, 285652-285917, 285932-286330,286335-286345, 286357-286358, 286383-286403, 286419-286421,286428-287111, 287126-287182, 287205-287278, 287292-287308,287322-287354, 287368-287423, 287437-287469, 287488-287829,287843-287904, 287919-287976, 287990-288075, 288091-288120,288135-288171, 288185-288255, 288269-288474, 288488-288521,288535-288825, 288839-288973, 288987-289088, 289102-289127,289142-289149, 289163-289294, 289310-289578, 289592-289649,289663-289683, 289698-289866, 289881-289887, 289901-290032,290046-290052, 290066-290444, 290474-290773, 290787-290812,290826-291164, 291178-291189, 291214-291223, 291237-291453,291467-291484, 291524-291766, 291780-291907, 291922-291943,291962-291996, 292010-292140, 292154-292302, 292318-292477,292491-292495, 292510-292556, 292570-292584, 292599-292828,292842-293028, 293042-293046, 293060-293258, 293273-293285,293288-293303, 293306-293641, 293656-293742, 293757-293906,293921-294024, 294038-294047, 294061-294377, 294391-294450,294475-294922, 294936-294954, 294968-295019, 295028-295061,295072-295291, 295305-295342, 295350-295606, 295620-295685,295689-295964, 295978-296012, 296014-296047, 296052-296059,296071-296087, 296118-296137, 296152-296253, 296267-296302,296316-296356, 296374-296377, 296400-296493, 296508-296653,296667-296822, 296836-296968, 296982-297030, 297051-297098,297112-297283, 297297-297369, 297385-297395, 297409-297454,297468-297490, 297504-297609, 297626-297693, 297718-297818,297832-297840, 297854-297987, 298001-298174, 298188-298260,298274-298368, 298382-298421, 298435-298560, 298574-298821,298835-298962, 298976-299242, 299256-299340, 299354-299356,299370-299835, 299849-300472, 300496-300806, 300820-300854,300869-301030, 301044-301085, 301106-301107, 301121-301438,301453-301558, 301573-301580, 301594-301607, 301621-301807,301823-301970, 301984-302064, 302078-302144, 302160-302163,302187-302302, 302316-302491, 302510-302555, 302569-302615,302629-302727, 302741-303035, 303049-303135, 303149-303169,303183-303265, 303279-303369, 303383-303427, 303441-303507,303521-303653, 303667-304191, 304205-304225, 304239-304701,304716-305241, 305255-305269, 305284-305427, 305441-305501,305515-305549, 305561-305794, 305812-306017, 306020-306042,306049-306054, 306057-306106, 306108-306112, 306115-306132,306138-306149, 306163-306164, 306179-306216, 306225-306228,306230-306247, 306250-306302, 306305-306310, 306312-306329,306335-306346, 306354-306379, 306382-306394, 306396-306422,306427-306433, 306435-306502, 306506-306520, 306522-306531, 306534,306541-306544, 306548-306550, 306556-306597, 306602-306623,306630-306659, 306664-306685, 306687-306690, 306693-306697,306699-306703, 306715-306723, 306728-306736, 306738-306749,306752-306782, 306788-306798, 306803-306804, 306807, 306814-306815,306833-306854, 306856-306858, 306862-306864, 306867-306869,306871-306905, 306909, 306920-306952, 306963-307021, 307023-307037,307041-307048, 307052-307053, 307062-307063, 307067-307084,307086-307104, 307111-307113, 307115-307148, 307154-307164,307171-307286, 307295-307309, 307312-307314, 307316-307322,307324-307352, 307355-307388, 307392-307444, 307446-307644,307658-307679, 307694-307784, 307790-307882, 307888-307926,307928-307940, 307942-307975, 307977-307980

SeqIDs w/o miR Seeds:

467, 469-472, 474, 477, 479-484, 487-488, 491-494, 496-497, 504,506-508, 512-513, 515-518, 521-523, 525-526, 528, 530, 532, 536-544,546-554, 556-557, 561-567, 569-575, 577-582, 584-589, 592-596, 598-601,603-605, 609-613, 615, 617-618, 621-623, 625, 628, 630-634, 636-638,643, 645-647, 649, 651-653, 656, 659-664, 666, 668, 670, 672, 674-678,680, 682-689, 691-703, 706, 709-710, 712, 714-715, 718, 720-724,727-728, 730-733, 735-741, 743-747, 749-751, 753-754, 757-759, 761,764-766, 769-770, 772-773, 775-776, 778, 780-781, 783-786, 788-791, 793,795-801, 803, 805-808, 810-811, 813, 815-817, 823, 827-834, 837-840,842-844, 847-849, 851, 853-857, 859, 861, 863, 867-868, 871, 873-877,880-885, 887-888, 890, 893-897, 899-900, 903-904, 906-907, 910-911, 915,917-922, 927, 930-932, 937-939, 941, 943, 947-949, 951-953, 958-960,962-966, 968-970, 972-973, 975, 977, 979, 984, 988-990, 993-994,996-1005, 1008, 1011, 1013-1021, 1023-1024, 1027-1028, 1031, 1034,1036-1039, 1041-1042, 1045-1047, 1049, 1051, 1053-1054, 1056-1057,1059-1060, 1064, 1067, 1070, 1073-1077, 1079-1080, 1082-1085, 1087,1089, 1091, 1093-1096, 1100-1101, 1103, 1105, 1108-1117, 1119,1121-1123, 1126-1128, 1130-1133, 1137, 1139, 1141-1142, 1147, 1149-1154,1157, 1159, 1161-1162, 1165, 1167, 1169, 1171, 1173-1179, 1183-1185,1187, 1189, 1191-1197, 1199-1206, 1210-1212, 1214, 1216-1219, 1221,1224-1228, 1232, 1234-1235, 1241-1242, 1246-1247, 1249-1253, 1255-1258,1261-1268, 1272, 1274-1275, 1278, 1285, 1292-1294, 1296, 1298,1301-1304, 1307-1310, 1312, 1315-1318, 1320-1322, 1324, 1326-1328, 1331,1333-1334, 1337, 1340-1346, 1348-1349, 1353, 1357-1360, 1363, 1368-1374,1378-1381, 1383-1384, 1386, 1390-1391, 1393-1394, 1396-1397, 1400-1401,1403, 1405-1407, 1409, 1412-1414, 1416, 1424, 1427, 1429-1435,1437-1443, 1445, 1448, 1451-1455, 1457-1459, 1461, 1465-1466, 1469,1471-1472, 1474-1476, 1478-1487, 1489-1490, 1492, 1494, 1496-1497,1500-1502, 1504-1507, 1509, 1511, 1513, 1515-1516, 1518, 1520-1522,1524-1525, 1527-1533, 1535, 1537-1539, 1541-1543, 1545-1548, 1550-1552,1554, 1558-1560, 1562-1564, 1566-1568, 1572, 1575, 1577-1578, 1581-1582,1588, 1590, 1594, 1599, 1606-1617, 1619, 1624, 1626, 1628-1631, 1634,1637-1638, 1640, 1642-1644, 1648-1649, 1651-1652, 1654-1658, 1662-1664,1666, 1668-1669, 1672, 1674, 1676, 1678-1683, 1687-1692, 1695-1697,1699-1702, 1706-1707, 1710, 1712-1720, 1725, 1727-1733, 1735-1736,1738-1743, 1745, 1747, 1749-1751, 1753-1756, 1761-1763, 1765-1773,1776-1777, 1779-1786, 1788-1789, 1791-1793, 1795-1796, 1799-1801,1803-1804, 1808, 1810-1816, 1819-1820, 1824-1829, 1831-1833, 1835, 1837,1840-1841, 1845, 1849, 1852, 1854-1875, 1877, 1879, 1881, 1883-1884,1886-1887, 1891-1896, 1899-1900, 1905, 1909, 1914-1915, 1917-1919,1921-1922, 1928, 1931-1932, 1934-1936, 1938-1941, 1946, 1949, 1952-1958,1960, 1963-1964, 1969, 1972, 1976-1977, 1981, 1983, 1985-1987, 1989,1991-1995, 1997, 2003-2005, 2008, 2013-2020, 2026-2031, 2033, 2035-2038,2041-2042, 2044, 2046-2052, 2054-2059, 2061-2062, 2064, 2066-2070,2076-2078, 2081-2082, 2084, 2086-2087, 2089, 2092-2095, 2097-2098, 2100,2102, 2105, 2109, 2112, 2118, 2120, 2126-2129, 2131-2138, 2141-2142,2146, 2150, 2152-2153, 2155-2156, 2158-2160, 2162-2163, 2168-2172, 2174,2176, 2179, 2183, 2185, 2188-2189, 2191, 2193, 2196, 2200, 2202-2203,2205, 2207, 2209-2212, 2214-2219, 2221, 2223-2226, 2228, 2231, 2238,2241-2242, 2244, 2248-2250, 2252-2253, 2255-2256, 2259, 2261-2262,2264-2265, 2267, 2270-2272, 2277-2280, 2282-2283, 2285-2287, 2289-2297,2299-2302, 2304-2309, 2316, 2318-2319, 2325, 2327-2334, 2336, 2338-2339,2341-2343, 2345-2346, 2351, 2353-2356, 2358, 2360, 2362, 2364,2367-2373, 2376-2378, 2380-2383, 2386-2387, 2389-2392, 2395, 2400-2401,2403, 2406-2407, 2409, 2412, 2414, 2416-2422, 2425-2427, 2429-2433,2435, 2437-2439, 2444-2446, 2453-2456, 2458, 2461, 2463, 2465-2466,2468-2469, 2471-2476, 2478-2480, 2482-2483, 2485-2489, 2493, 2496-2497,2499, 2501-2505, 2507, 2509-2510, 2512, 2514-2515, 2517, 2519-2521,2523-2527, 2532, 2534, 2536-2538, 2540, 2545-2548, 2551-2552, 2554,2556-2557, 2560, 2562-2564, 2566-2568, 2570, 2573, 2575-2576, 2581-2587,2589-2594, 2596-2604, 2608-2613, 2615, 2619, 2622, 2624, 2626-2628,2630-2631, 2635, 2637-2638, 2640, 2642-2644, 2646-2647, 2650-2651,2654-2656, 2659-2663, 2665-2669, 2674, 2676-2681, 2683, 2685, 2687,2689-2691, 2693, 2697, 2699-2700, 2706, 2708-2709, 2711-2712, 2714-2715,2717, 2723-2727, 2729-2732, 2734-2742, 2744-2745, 2748, 2750-2751, 2753,2756, 2758-2759, 2765, 2767-2770, 2772, 2774, 2778, 2780, 2786, 2789,2794, 2796-2797, 2800-2801, 2803, 2805-2806, 2810, 2812-2815, 2821-2826,2829-2834, 2836-2837, 2839-2840, 2843-2855, 2859-2864, 2866, 2868-2870,2872-2873, 2876, 2878-2880, 2882-2885, 2892, 2894-2895, 2899, 2901,2903-2906, 2909-2911, 2916-2920, 2922-2925, 2930-2933, 2935, 2938, 2940,2945, 2947-2951, 2953-2958, 2960-2965, 2967-2969, 2971, 2974-2978,2981-2982, 2985-2988, 2991-2992, 2996-2998, 3000-3001, 3003, 3006, 3008,3013, 3015-3016, 3018-3021, 3023-3024, 3026-3032, 3035-3044, 3046, 3048,3050-3054, 3056-3068, 3071, 3074-3081, 3083, 3085-3088, 3090-3094,3099-3102, 3106-3112, 3114-3118, 3121-3123, 3125-3131, 3133-3138,3141-3144, 3146, 3150, 3153-3154, 3156, 3158, 3161-3162, 3164-3167,3172, 3174-3178, 3180-3182, 3184, 3186-3191, 3193, 3195, 3199,3202-3210, 3212-3214, 3218, 3220-3221, 3224, 3226-3227, 3230-3235,3238-3239, 3244-3247, 3249-3251, 3253, 3255-3260, 3262-3264, 3268,3270-3281, 3284-3286, 3288-3293, 3295-3301, 3303-3307, 3310, 3312-3317,3323-3325, 3333-3334, 3336, 3341-3345, 3348-3350, 3354-3355, 3359-3368,3372, 3375, 3377-3379, 3382, 3384-3386, 3389, 3391, 3393-3395,3399-3403, 3405-3406, 3408, 3410, 3415-3417, 3419-3421, 3424, 3426,3428, 3430-3432, 3434, 3436-3438, 3440-3443, 3445-3446, 3449, 3452-3453,3457, 3461-3463, 3466, 3469-3472, 3475, 3477-3478, 3480, 3482, 3486,3490, 3492-3497, 3499-3501, 3503, 3505, 3510-3511, 3513, 3515-3522,3524-3525, 3530-3534, 3536, 3539-3544, 3546-3550, 3552-3553, 3557, 3564,3566-3567, 3570-3574, 3576-3577, 3579-3581, 3583-3585, 3589, 3592, 3599,3601, 3603, 3605-3608, 3610-3612, 3615-3620, 3622, 3625-3633, 3636-3648,3650-3651, 3653-3657, 3659, 3661, 3667-3669, 3671-3673, 3675-3676,3678-3682, 3684, 3686-3687, 3690-3693, 3700-3701, 3704-3705, 3709, 3711,3714, 3718, 3722-3725, 3727-3728, 3730-3734, 3736-3743, 3746-3749,3752-3753, 3759-3761, 3764, 3768, 3771, 3773-3776, 3778-3779, 3782,3784-3785, 3789-3790, 3792, 3795, 3799, 3806, 3810-3811, 3813, 3817,3820-3823, 3828, 3831, 3833-3835, 3837-3838, 3840-3842, 3844, 3848-3854,3856-3859, 3861, 3863-3864, 3868, 3874-3875, 3877-3880, 3882, 3886-3890,3896-3901, 3904-3907, 3910, 3912, 3914-3919, 3921-3937, 3939-3940,3942-3943, 3945-3951, 3955, 3959-3963, 3966-3968, 3973, 3975, 3982-3983,3985, 3987-3988, 3990-3991, 3993-3998, 4004, 4008-4009, 4011-4014,4016-4017, 4024-4025, 4028, 4030-4031, 4033-4034, 4038, 4040, 4045,4048, 4050-4052, 4055-4057, 4059, 4061-4065, 4068-4072, 4077-4079,4081-4082, 4084, 4086, 4088, 4092, 4094, 4096-4097, 4101-4105, 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304205-304208, 304210-304212,304214-304224, 304226, 304233, 304235-304240, 304244, 304247-304250,304252-304255, 304257-304261, 304263, 304266-304267, 304269-304270,304274-304276, 304278-304283, 304285-304289, 304292-304293,304295-304297, 304300-304304, 304306, 304311-304315, 304318, 304321,304323-304328, 304334-304338, 304340-304341, 304343-304344,304346-304350, 304352, 304354-304355, 304357-304359, 304361-304363,304365, 304367, 304369-304374, 304377, 304380-304382, 304384-304386,304388, 304391-304405, 304409, 304413-304418, 304420-304425, 304427,304429-304436, 304438-304439, 304442-304444, 304448-304449,304452-304453, 304455-304460, 304463-304469, 304471-304473,304475-304478, 304480-304481, 304483-304485, 304488-304492, 304495,304499, 304501-304503, 304505-304508, 304511-304513, 304515-304519,304521-304525, 304527-304529, 304532, 304535-304537, 304539-304540,304544-304546, 304548-304550, 304554-304556, 304561-304563, 304565,304570-304571, 304573-304574, 304576, 304580-304581, 304584,304587-304588, 304590-304591, 304593-304600, 304602-304613,304616-304620, 304623-304624, 304626, 304629-304630, 304632-304634,304637, 304639, 304641-304642, 304645-304646, 304654, 304657,304660-304661, 304663-304664, 304667-304668, 304670, 304672-304675,304678, 304682, 304685, 304687-304689, 304691-304692, 304694-304697,304699-304701, 304703, 304707-304708, 304710-304718, 304721,304723-304724, 304726, 304728-304729, 304732, 304735, 304737-304738,304740, 304742-304746, 304748-304749, 304755-304757, 304759,304761-304773, 304776-304778, 304780-304782, 304785, 304788-304794,304796-304800, 304803, 304805, 304807-304811, 304813, 304815, 304818,304820-304821, 304823-304827, 304829-304830, 304832-304838, 304841,304845-304854, 304856-304857, 304860-304868, 304871-304873, 304875,304877-304879, 304881-304882, 304884-304891, 304895-304896,304898-304899, 304901-304903, 304905-304908, 304910-304911, 304918,304921-304925, 304930-304931, 304933-304948, 304950-304951,304953-304956, 304960, 304963, 304967, 304969-304972, 304974, 304976,304978, 304980-304991, 304995-305002, 305005-305008, 305010-305012,305015-305017, 305019, 305022-305032, 305034-305035, 305037-305042,305044, 305046-305048, 305050, 305052-305064, 305066, 305069-305076,305078-305080, 305082, 305084-305086, 305089, 305091-305095, 305097,305100, 305102-305103, 305105-305106, 305112, 305114-305118,305122-305128, 305130-305133, 305135, 305137-305138, 305141-305145,305150-305151, 305153, 305158-305161, 305163-305165, 305169-305170,305172-305177, 305179-305180, 305183-305184, 305186, 305188-305191,305193-305196, 305198-305200, 305202, 305204, 305206-305209, 305214,305216, 305218-305221, 305223, 305227-305228, 305230, 305236, 305238,305241-305243, 305245, 305247, 305249-305250, 305252-305254,305257-305258, 305260, 305263, 305266-305271, 305274-305275,305277-305278, 305281-305284, 305287, 305289-305291, 305293-305299,305302-305303, 305305-305306, 305308-305310, 305314-305317,305319-305320, 305322, 305324, 305328-305330, 305332-305333, 305335,305337-305344, 305346-305349, 305351, 305354-305357, 305359-305362,305365-305372, 305374, 305376, 305378-305387, 305389-305390,305392-305398, 305400-305401, 305404-305406, 305408, 305410-305411,305414, 305417-305422, 305428, 305432-305434, 305436-305437,305444-305445, 305447-305448, 305450, 305452-305456, 305458-305462,305468, 305471-305474, 305476, 305478-305480, 305486-305487,305491-305492, 305494, 305497-305502, 305504, 305508, 305512,305514-305529, 305532, 305534, 305536-305539, 305541-305542,305544-305545, 305549, 305551-305552, 305554, 305557-305558,305560-305573, 305575-305576, 305579-305581, 305583, 305585-305595,305597-305598, 305602-305603, 305608, 305610-305617, 305619,305621-305622, 305624, 305626-305628, 305630, 305632, 305634, 305636,305638, 305643-305645, 305647-305650, 305652, 305658-305666,305668-305670, 305675, 305679, 305682-305684, 305687-305691,305694-305698, 305701-305721, 305724-305730, 305732-305740,305743-305746, 305749-305751, 305753, 305755-305756, 305759-305769,305772, 305774-305776, 305778, 305783-305784, 305786-305788,305790-305793, 305796, 305802, 305805-305807, 305809, 305811, 305813,305815, 305818-305820, 305822, 305826, 305829-305835, 305837-305838,305843-305847, 305849, 305851-305857, 305859, 305862, 305865-305869,305871, 305874-305875, 305879-305881, 305886-305887, 305891-305899,305902-305905, 305908-305910, 305912-305916, 305918-305921,305923-305925, 305927, 305929, 305931-305932, 305936-305938, 305942,305944-305945, 305948-305949, 305951-305952, 305955-305957, 305960,305964-305965, 305967-305977, 305979, 305981-305982, 305984, 305986,305988-305991, 305994-305995, 305998, 306002, 306005, 306008-306015,306017, 306020-306021, 306023, 306025, 306027-306033, 306035-306038,306040-306041, 306043-306045, 306053-306055, 306063-306065,306067-306068, 306073, 306077, 306079-306084, 306088-306097, 306099,306103, 306105-306106, 306112-306113, 306115-306118, 306121,306123-306124, 306127, 306130, 306133-306134, 306138-306140,306143-306146, 306152-306155, 306164-306165, 306167, 306173-306176,306180-306187, 306191, 306194-306196, 306199-306202, 306205-306207,306209-306210, 306215-306222, 306225-306226, 306231, 306233-306234,306236-306238, 306240-306241, 306244-306245, 306247, 306251-306252,306254-306262, 306265, 306270, 306274-306276, 306278-306279,306281-306282, 306285, 306288-306289, 306291, 306295, 306297-306298,306300, 306302-306303, 306306-306312, 306314, 306317, 306321-306322,306324-306328, 306333, 306337, 306339-306341, 306343-306344,306346-306347, 306349-306354, 306356-306359, 306363, 306365, 306369,306372-306376, 306378-306380, 306382-306386, 306390-306393,306395-306403, 306406-306407, 306411-306412, 306415-306417,306419-306420, 306425-306429, 306431-306439, 306441, 306443-306449,306452, 306455-306468, 306471, 306473-306479, 306481, 306483, 306486,306488-306489, 306491, 306493-306494, 306498, 306503, 306505-306507,306509, 306511-306517, 306519-306520, 306522, 306524, 306526, 306529,306534-306535, 306537, 306542, 306544, 306547, 306549, 306551,306553-306555, 306557-306558, 306562, 306565, 306568, 306571, 306573,306575, 306577, 306579-306581, 306583, 306585, 306589-306590,306592-306593, 306595, 306597, 306599, 306601-306603, 306605,306608-306610, 306615-306616, 306618, 306621-306622, 306628, 306630,306633-306635, 306638, 306641-306643, 306646-306649, 306653,306655-306658, 306664, 306666-306669, 306673-306677, 306680-306681,306683-306684, 306688-306693, 306695, 306699-306701, 306703-306704,306706, 306708, 306710, 306713, 306716-306717, 306719, 306721-306722,306725, 306728-306730, 306735, 306737-306741, 306743-306749,306751-306752, 306754-306755, 306757, 306759-306761, 306763-306764,306766-306768, 306770, 306772, 306774-306776, 306778, 306781,306783-306788, 306791, 306796-306804, 306806-306808, 306815-306816,306821-306824, 306826, 306828-306829, 306831-306835, 306838-306840,306843-306844, 306846-306848, 306850-306851, 306853-306854,306856-306858, 306863-306865, 306867, 306869, 306872-306874,306878-306880, 306886-306887, 306891-306896, 306898, 306900-306901,306903-306904, 306907, 306909-306911, 306913, 306917, 306920, 306922,306924-306928, 306930, 306933-306941, 306943-306946, 306948-306949,306951-306955, 306957-306961, 306964-306966, 306971-306974,306976-306978, 306980, 306983-306985, 306987-306988, 306991-306993,306996, 306998, 307001-307008, 307010-307011, 307014-307015,307017-307019, 307021, 307023, 307025, 307028-307033, 307038-307040,307042-307045, 307049, 307051, 307057-307062, 307065-307066,307068-307069, 307072-307075, 307077-307080, 307082-307084, 307087,307089-307090, 307093-307100, 307102-307106, 307108-307113,307117-307119, 307121-307122, 307124, 307126-307127, 307129-307135,307137-307138, 307141-307145, 307148-307149, 307152-307155,307157-307165, 307172-307174, 307176, 307182-307198, 307200-307201,307203-307205, 307209-307210, 307213-307215, 307218-307220,307223-307224, 307227-307229, 307231, 307233-307235, 307237-307240,307242, 307246-307248, 307251-307253, 307255-307259, 307262,307264-307265, 307267-307270, 307272, 307274-307278, 307280, 307282,307284-307287, 307289, 307292, 307295, 307297-307299, 307301-307303,307305-307310, 307312, 307314, 307316, 307318-307328, 307330-307331,307335, 307341, 307343-307346, 307352, 307357-307360, 307363-307375,307377, 307380-307381, 307383-307388, 307390, 307392-307397,307399-307402, 307404-307405, 307407-307409, 307412, 307415, 307417,307419-307431, 307433-307436, 307438, 307441-307443, 307447-307448,307452-307453, 307455-307458, 307461-307462, 307464, 307466-307467,307469, 307471, 307473-307476, 307478-307480, 307482, 307484-307485,307487-307493, 307495-307507, 307509, 307511-307513, 307515-307524,307526-307527, 307530-307532, 307534-307543, 307545-307548,307552-307553, 307555-307558, 307561, 307563-307569, 307571, 307573,307577-307579, 307582-307583, 307585, 307587, 307591-307593,307595-307597, 307599-307600, 307602, 307604-307606, 307608,307611-307621, 307623-307628, 307631, 307634-307636, 307638-307643,307645, 307649-307651, 307658-307660, 307662, 307665-307666,307670-307677, 307679-307685, 307692-307693, 307696-307697,307699-307700, 307702-307707, 307709-307710, 307712-307722,307724-307727, 307729-307730, 307732-307733, 307735-307741,307744-307746, 307748-307752, 307754, 307757-307764, 307766-307768,307770-307773, 307775-307781, 307785-307788, 307790-307791, 307796,307799, 307801-307804, 307807, 307809-307813, 307816-307819, 307821,307827-307832, 307834-307839, 307841-307848, 307850-307868, 307876,307878-307880, 307882-307883, 307885-307889, 307891, 307893-307894,307897, 307899-307900, 307902, 307905-307907, 307909, 307913-307916,307918-307920, 307922-307924, 307928, 307931, 307933, 307935-307937,307939-307940, 307944-307945, 307947, 307949, 307951-307955,307959-307960, 307962-307965, 307970, 307972, 307974-307980

Single Strand Oligonucleotides (Sense Strand of Target Gene)

SegID range: 306018-497728

SegIDs w/o G Runs:

306020-306042, 306049-306054, 306057-306106, 306108-306112,306115-306132, 306138-306149, 306163-306164, 306179-306216,306225-306228, 306230-306247, 306250-306302, 306305-306310,306312-306329, 306335-306346, 306354-306379, 306382-306394,306396-306422, 306427-306433, 306435-306502, 306506-306520,306522-306531, 306534, 306541-306544, 306548-306550, 306556-306597,306602-306623, 306630-306659, 306664-306685, 306687-306690,306693-306697, 306699-306703, 306715-306723, 306728-306736,306738-306749, 306752-306782, 306788-306798, 306803-306804, 306807,306814-306815, 306833-306854, 306856-306858, 306862-306864,306867-306869, 306871-306905, 306909, 306920-306952, 306963-307021,307023-307037, 307041-307048, 307052-307053, 307062-307063,307067-307084, 307086-307104, 307111-307113, 307115-307148,307154-307164, 307171-307286, 307295-307309, 307312-307314,307316-307322, 307324-307352, 307355-307388, 307392-307444,307446-307644, 307658-307679, 307694-307784, 307790-307882,307888-307926, 307928-307940, 307942-307975, 307977-307980,307997-308001, 308016-308023, 308038-308085, 308111-308124, 308138,308153-308154, 308170-308181, 308203-308261, 308284-308344,308359-308360, 308373-308436, 308457-308463, 308477-308480,308495-308516, 308541-308550, 308564-308678, 308693, 308707-308854,308869-308893, 308907-308928, 308942-308956, 308988-309010,309024-309055, 309069-309083, 309098-309141, 309155-309157,309171-309241, 309256-309279, 309300-309305, 309320-309344,309374-309385, 309410-309449, 309464-309469, 309483-309488,309507-309553, 309583-309626, 309641-309676, 309691-309800,309814-309832, 309846-309867, 309881-309905, 309919-309948,309962-309988, 310011-310021, 310039-310067, 310083-310118,310132-310177, 310191-310201, 310221-310233, 310254-310268,310282-310291, 310305-310335, 310349-310368, 310382-310830,310844-310905, 310934-310952, 310966-311057, 311081-311300,311314-311393, 311407-311442, 311456-311459, 311473-311571,311585-311939, 311942-311974, 311976-312015, 312029-312073,312083-312921, 312935-312995, 312998-313018, 313027-313437,313451-313868, 313882-314226, 314240-314459, 314474-314543,314558-314648, 314663-315017, 315031-315137, 315151-315832,315846-316025, 316058-316076, 316090-316096, 316110-316111,316124-316158, 316173-316198, 316212-316222, 316236-316242,316256-316286, 316302-316615, 316629-316652, 316666-316719,316734-316746, 316761-316765, 316779-316826, 316854-316906,316931-316991, 317019-317056, 317070-317106, 317126-317208,317222-317251, 317261-317316, 317337-317353, 317367-317370,317379-317410, 317423-317635, 317649-317681, 317708-317776,317790-317863, 317877-317933, 317947-318052, 318066-318212,318226-318324, 318338-318555, 318569-318642, 318656-318755,318769-318780, 318803-318877, 318889-319319, 319333-319506,319520-320079, 320095-320146, 320161-320309, 320330-320353,320367-320651, 320670-320764, 320779-320800, 320814-320938,320952-320968, 320982-321111, 321126-321134, 321141-321223,321234-321312, 321326-321726, 321741-321811, 321839-321857,321871-322082, 322096-322122, 322137-322228, 322242-322361,322380-322460, 322474-322567, 322604-322834, 322864-322964,322991-323056, 323070-323081, 323095-323194, 323208-323239,323253-323279, 323293-323336, 323350-323436, 323450-323515,323529-323564, 323578-323622, 323636-323693, 323714-323727,323752-323776, 323794-323817, 323830-323831, 323844-323852,323867-323919, 323934-323966, 323980-324049, 324063-324088,324102-324166, 324180-324194, 324208-324209, 324223-324338,324353-324392, 324406-324624, 324638-324791, 324797-324932,324949-324961, 324970-324984, 324991-325063, 325069-325582,325596-325614, 325628-325734, 325748-325772, 325798-325817,325829-325866, 325880-325950, 325964-325968, 325981-326039,326054-326065, 326079-326444, 326458-326483, 326506-326576,326591-326623, 326637-326853, 326867-327076, 327090-327174,327189-327353, 327367-327609, 327623, 327637-327778, 327822-327882,327896-327936, 327950-327961, 327975-327979, 328008-328208,328222-328260, 328274-329045, 329059-329437, 329455-329565,329579-329603, 329617-329632, 329646-329675, 329689-329696,329710-329714, 329728-329746, 329760-329777, 329798-329903,329918-330225, 330239-330336, 330360-330377, 330391-330503,330517-330639, 330663-330717, 330731-330766, 330780-331138,331145-331210, 331215-331372, 331386-331398, 331412-331522,331536-331821, 331834-331909, 331919-331945, 331949-331984,331998-332011, 332015-332050, 332064-332083, 332097-332220,332234-332435, 332452-332538, 332552-332582, 332596-332625,332639-332683, 332697-332852, 332869-332906, 332920-332990,333004-333085, 333099-333113, 333127-333149, 333159-333206,333220-333242, 333245-333285, 333319-333363, 333371-333376,333390-333975, 333988-334010, 334016-334063, 334076-334433,334448-334547, 334561-334696, 334698-334752, 334766-334850,334864-334891, 334905-335417, 335437-335475, 335489-335520,335535-335636, 335655-336575, 336589-336703, 336717-337484,337498-337683, 337697-337791, 337805-337924, 337938-338003,338018-338029, 338043-338094, 338108-338195, 338209-338220, 338246,338273-338280, 338298-338436, 338460-338705, 338719-338849,338863-338997, 339005-339058, 339072-339289, 339297-339324,339335-339368, 339372-339720, 339734-339824, 339850-339997,340011-340120, 340133-340148, 340158-340172, 340186-340194,340198-340252, 340256-340290, 340305-340525, 340539-340644,340658-340702, 340716-340992, 341006, 341020-341032, 341046-341068,341091-341149, 341163-341210, 341224-341277, 341295-341497,341511-341539, 341542-341565, 341578-341580, 341594-341693,341707-341882, 341900-342018, 342032-342297, 342311-342369,342383-342406, 342421-342423, 342437-342468, 342496-342592,342606-342635, 342643-342744, 342759-342893, 342907-343048,343061-343127, 343138-343199, 343204-343527, 343544-343653,343667-343679, 343693-343809, 343830-343913, 343928-343962,343976-344005, 344025-344212, 344226-344266, 344280-344488,344503-344701, 344716-344830, 344844-344901, 344915-345481,345496-345528, 345556-345564, 345592-345768, 345783-346146,346160-346315, 346330-346531, 346545-346607, 346621-346647,346661-346917, 346938-346999, 347014-347429, 347443-347637,347651-347816, 347830-347835, 347849-348068, 348082-348368,348382-348495, 348509-348599, 348613-348701, 348716-348720,348734-349089, 349103-349128, 349131-349160, 349174-349198,349203-349296, 349310-349867, 349881-350079, 350101-350133,350147-350175, 350189-350237, 350251-350300, 350314-350421,350436-350530, 350544-350806, 350820-351095, 351109-351120,351134-351253, 351268-351287, 351301-351615, 351635-351708,351722-351732, 351744-352173, 352187-352192, 352207-352283,352297-352430, 352444-352481, 352496-352597, 352611-352616,352630-352831, 352845-352925, 352939-353117, 353131-353314,353317-353347, 353353-353384, 353400-353594, 353609-354202,354217-354871, 354885-355050, 355064-355229, 355256-355280,355294-355306, 355320-355382, 355396-355557, 355580-355590,355604-355609, 355624-355713, 355727-355795, 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458173-458204,458218-458245, 458260-458346, 458361-458620, 458634-458659,458675-458698, 458713-458717, 458731-458833, 458846-458992,459006-459062, 459076-459370, 459385-459472, 459486-459718,459733-459775, 459789-459795, 459809-459835, 459849-459877,459901-460073, 460088-460476, 460491-460871, 460885-461220,461234-461498, 461512-461589, 461603-461629, 461643-461807,461822-461909, 461923-461973, 461987-462014, 462028-462104,462118-462227, 462241-462298, 462312-462373, 462387-462431,462445-463129, 463143-463258, 463272-463370, 463385-463543,463557-463584, 463598-463888, 463902-464205, 464219-464561,464575-465250, 465263-465331, 465345-465591, 465605-466000, 466014,466053-466166, 466189-466273, 466287-466337, 466351-466418,466433-466450, 466475-466525, 466548-466725, 466740-466934,466948-466955, 466969-466985, 467000-467045, 467062-467131,467145-467196, 467232-467315, 467330-467341, 467357-469068,469083-469187, 469201-469413, 469427-469451, 469466-469678,469692-470136, 470150-470353, 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481400-481548, 481562-481564, 481580-481857,481871-481984, 481998-482388, 482402-482567, 482581-482854,482868-482969, 482983-482993, 483007-483098, 483112-483166,483180-483291, 483305-483320, 483336-483344, 483358-483560,483576-483757, 483771-483809, 483823-484059, 484073-484234,484248-484449, 484463-484590, 484604-484699, 484714-485037,485051-485069, 485083-485106, 485108-485280, 485294-485446,485465-485566, 485580-486138, 486153-486265, 486279-486329,486336-486362, 486369-486782, 486796-486814, 486828-486871,486885-486938, 486952-487216, 487232-487270, 487284-487480,487494-487640, 487655-487920, 487934-488009, 488031-488079,488088-488113, 488121-488136, 488143-488443, 488451-488464,488469-488492, 488502-488921, 488936-488984, 488998-489467,489481-489588, 489602-489712, 489725-489754, 489768-489823,489837-490416, 490431-490812, 490826-491020, 491034-491054,491068-491184, 491198-491227, 491243-491288, 491303-491368,491382-491454, 491479-491553, 491597-491780, 491794-491883,491897-492178, 492201-492398, 492413-492535, 492549-492614,492628-492645, 492661-492762, 492780-492832, 492846-492860,492887-492908, 492922-493011, 493025-493180, 493194-493201,493215-493220, 493235-493237, 493251-493284, 493323-493387,493401-493457, 493471-493512, 493526-493545, 493560-493576,493590-493658, 493672-493677, 493691-493728, 493743-493841,493855-493879, 493893-493924, 493938-493949, 493963-493996,494010-494165, 494183-494627, 494655-495051, 495065-495438,495452-495740, 495754-495755, 495769-495812, 495844-496225,496239-496769, 496783-497095, 497109-497179, 497193-497201,497215-497728

SeqIDs w/o miR Seeds:

306020-306021, 306023, 306025, 306027-306033, 306035-306038,306040-306041, 306043-306045, 306053-306055, 306063-306065,306067-306068, 306073, 306077, 306079-306084, 306088-306097, 306099,306103, 306105-306106, 306112-306113, 306115-306118, 306121,306123-306124, 306127, 306130, 306133-306134, 306138-306140,306143-306146, 306152-306155, 306164-306165, 306167, 306173-306176,306180-306187, 306191, 306194-306196, 306199-306202, 306205-306207,306209-306210, 306215-306222, 306225-306226, 306231, 306233-306234,306236-306238, 306240-306241, 306244-306245, 306247, 306251-306252,306254-306262, 306265, 306270, 306274-306276, 306278-306279,306281-306282, 306285, 306288-306289, 306291, 306295, 306297-306298,306300, 306302-306303, 306306-306312, 306314, 306317, 306321-306322,306324-306328, 306333, 306337, 306339-306341, 306343-306344,306346-306347, 306349-306354, 306356-306359, 306363, 306365, 306369,306372-306376, 306378-306380, 306382-306386, 306390-306393,306395-306403, 306406-306407, 306411-306412, 306415-306417,306419-306420, 306425-306429, 306431-306439, 306441, 306443-306449,306452, 306455-306468, 306471, 306473-306479, 306481, 306483, 306486,306488-306489, 306491, 306493-306494, 306498, 306503, 306505-306507,306509, 306511-306517, 306519-306520, 306522, 306524, 306526, 306529,306534-306535, 306537, 306542, 306544, 306547, 306549, 306551,306553-306555, 306557-306558, 306562, 306565, 306568, 306571, 306573,306575, 306577, 306579-306581, 306583, 306585, 306589-306590,306592-306593, 306595, 306597, 306599, 306601-306603, 306605,306608-306610, 306615-306616, 306618, 306621-306622, 306628, 306630,306633-306635, 306638, 306641-306643, 306646-306649, 306653,306655-306658, 306664, 306666-306669, 306673-306677, 306680-306681,306683-306684, 306688-306693, 306695, 306699-306701, 306703-306704,306706, 306708, 306710, 306713, 306716-306717, 306719, 306721-306722,306725, 306728-306730, 306735, 306737-306741, 306743-306749,306751-306752, 306754-306755, 306757, 306759-306761, 306763-306764,306766-306768, 306770, 306772, 306774-306776, 306778, 306781,306783-306788, 306791, 306796-306804, 306806-306808, 306815-306816,306821-306824, 306826, 306828-306829, 306831-306835, 306838-306840,306843-306844, 306846-306848, 306850-306851, 306853-306854,306856-306858, 306863-306865, 306867, 306869, 306872-306874,306878-306880, 306886-306887, 306891-306896, 306898, 306900-306901,306903-306904, 306907, 306909-306911, 306913, 306917, 306920, 306922,306924-306928, 306930, 306933-306941, 306943-306946, 306948-306949,306951-306955, 306957-306961, 306964-306966, 306971-306974,306976-306978, 306980, 306983-306985, 306987-306988, 306991-306993,306996, 306998, 307001-307008, 307010-307011, 307014-307015,307017-307019, 307021, 307023, 307025, 307028-307033, 307038-307040,307042-307045, 307049, 307051, 307057-307062, 307065-307066,307068-307069, 307072-307075, 307077-307080, 307082-307084, 307087,307089-307090, 307093-307100, 307102-307106, 307108-307113,307117-307119, 307121-307122, 307124, 307126-307127, 307129-307135,307137-307138, 307141-307145, 307148-307149, 307152-307155,307157-307165, 307172-307174, 307176, 307182-307198, 307200-307201,307203-307205, 307209-307210, 307213-307215, 307218-307220,307223-307224, 307227-307229, 307231, 307233-307235, 307237-307240,307242, 307246-307248, 307251-307253, 307255-307259, 307262,307264-307265, 307267-307270, 307272, 307274-307278, 307280, 307282,307284-307287, 307289, 307292, 307295, 307297-307299, 307301-307303,307305-307310, 307312, 307314, 307316, 307318-307328, 307330-307331,307335, 307341, 307343-307346, 307352, 307357-307360, 307363-307375,307377, 307380-307381, 307383-307388, 307390, 307392-307397,307399-307402, 307404-307405, 307407-307409, 307412, 307415, 307417,307419-307431, 307433-307436, 307438, 307441-307443, 307447-307448,307452-307453, 307455-307458, 307461-307462, 307464, 307466-307467,307469, 307471, 307473-307476, 307478-307480, 307482, 307484-307485,307487-307493, 307495-307507, 307509, 307511-307513, 307515-307524,307526-307527, 307530-307532, 307534-307543, 307545-307548,307552-307553, 307555-307558, 307561, 307563-307569, 307571, 307573,307577-307579, 307582-307583, 307585, 307587, 307591-307593,307595-307597, 307599-307600, 307602, 307604-307606, 307608,307611-307621, 307623-307628, 307631, 307634-307636, 307638-307643,307645, 307649-307651, 307658-307660, 307662, 307665-307666,307670-307677, 307679-307685, 307692-307693, 307696-307697,307699-307700, 307702-307707, 307709-307710, 307712-307722,307724-307727, 307729-307730, 307732-307733, 307735-307741,307744-307746, 307748-307752, 307754, 307757-307764, 307766-307768,307770-307773, 307775-307781, 307785-307788, 307790-307791, 307796,307799, 307801-307804, 307807, 307809-307813, 307816-307819, 307821,307827-307832, 307834-307839, 307841-307848, 307850-307868, 307876,307878-307880, 307882-307883, 307885-307889, 307891, 307893-307894,307897, 307899-307900, 307902, 307905-307907, 307909, 307913-307916,307918-307920, 307922-307924, 307928, 307931, 307933, 307935-307937,307939-307940, 307944-307945, 307947, 307949, 307951-307955,307959-307960, 307962-307965, 307970, 307972, 307974-307980, 307983,307989-307991, 307995, 307997-308003, 308005-308011, 308017-308020,308022-308024, 308026-308027, 308029-308030, 308038-308039, 308042,308044, 308046-308053, 308055-308056, 308058-308059, 308061-308062,308064-308074, 308078-308082, 308084-308089, 308091-308092,308095-308096, 308098-308100, 308102, 308105, 308110-308114,308116-308117, 308119-308123, 308125, 308129-308132, 308136,308138-308140, 308143, 308146, 308152-308156, 308158, 308160-308163,308171-308172, 308174-308175, 308177-308180, 308185, 308187, 308190,308192-308193, 308195, 308197-308198, 308204-308212, 308214, 308217,308219-308220, 308223-308225, 308227, 308230, 308233-308238, 308240,308248, 308250-308252, 308254, 308257-308260, 308265, 308267-308269,308271, 308274, 308282, 308284-308285, 308288, 308291-308294, 308296,308298, 308300-308302, 308304-308306, 308309-308311, 308315, 308317,308319, 308321, 308324, 308326-308327, 308329, 308331-308332,308336-308339, 308342-308345, 308347-308348, 308351-308353, 308359,308364-308368, 308386, 308388-308390, 308392, 308396-308400, 308402,308405-308406, 308408-308414, 308416, 308420-308422, 308424,308428-308435, 308437-308438, 308440-308441, 308450-308451, 308454,308463-308469, 308471-308472, 308474, 308478-308479, 308482-308483,308485-308489, 308494, 308504, 308506, 308508, 308510-308512,308515-308517, 308519-308523, 308525, 308530, 308533-308536,308540-308542, 308544, 308546-308547, 308549-308550, 308552,308555-308563, 308566-308568, 308570, 308573-308574, 308577-308578,308582, 308585, 308588-308592, 308594-308595, 308597, 308599,308604-308607, 308613, 308616-308617, 308620, 308622, 308624-308626,308629, 308631-308633, 308635-308638, 308640, 308642-308643,308645-308649, 308651-308653, 308656-308659, 308661-308663,308674-308676, 308678-308680, 308682, 308684-308687, 308692-308695,308698-308704, 308706, 308708-308714, 308717-308734, 308737-308741,308743-308746, 308752, 308759-308761, 308763-308788, 308790-308797,308800-308801, 308803-308810, 308813-308814, 308816-308817,308819-308822, 308824-308827, 308829-308830, 308833-308834,308836-308840, 308842-308843, 308854-308855, 308857, 308860-308861,308863-308865, 308867, 308869-308870, 308872-308873, 308875-308878,308880, 308882-308885, 308887, 308889-308890, 308901-308902, 308904,308911-308917, 308919-308921, 308924, 308927-308930, 308933-308937,308939, 308944-308948, 308950, 308952-308954, 308956-308957,308961-308962, 308964-308965, 308975, 308980-308981, 308983-308985,308994, 308996, 308998, 309000-309002, 309004-309006, 309012-309013,309016, 309023-309025, 309027-309030, 309032, 309035, 309038-309039,309042-309045, 309047-309048, 309051-309053, 309057-309060,309063-309065, 309067-309069, 309071-309073, 309075-309076,309078-309082, 309085-309086, 309088, 309090-309093, 309095,309098-309099, 309101, 309103-309112, 309114-309115, 309119,309121-309125, 309127-309129, 309131-309133, 309135, 309139-309142,309145-309146, 309148, 309150, 309154-309157, 309160-309163, 309170,309173, 309175-309177, 309179-309182, 309185, 309187-309201,309205-309206, 309209-309210, 309212-309213, 309216-309222, 309225,309228-309237, 309239-309240, 309243-309246, 309248-309252,309254-309255, 309257-309258, 309263-309265, 309269, 309271,309274-309280, 309282, 309285, 309292-309294, 309299-309300,309304-309307, 309309-309310, 309313-309314, 309316, 309319-309321,309324, 309328-309330, 309333, 309338-309343, 309345-309346,309348-309351, 309354-309355, 309358, 309360, 309367, 309373-309379,309381-309382, 309384-309388, 309391, 309393-309396, 309400, 309402,309405-309407, 309409-309410, 309413-309414, 309417-309421, 309423,309425-309427, 309430-309431, 309433-309434, 309436-309438,309440-309444, 309448-309450, 309452-309457, 309463-309467,309470-309472, 309474-309476, 309479, 309484-309489, 309491-309492,309494-309499, 309506-309509, 309519-309520, 309522-309529,309531-309532, 309534-309535, 309541, 309543-309546, 309552,309555-309556, 309560, 309564, 309566-309568, 309575, 309583-309584,309586-309592, 309594-309598, 309602, 309604-309616, 309618-309619,309621-309626, 309628, 309630-309631, 309640, 309644-309649, 309651,309653-309654, 309657-309658, 309662-309665, 309668-309676, 309678,309680-309681, 309684, 309686-309687, 309689-309694, 309698-309700,309702-309705, 309707-309708, 309713, 309715-309717, 309719-309720,309724-309726, 309729, 309732, 309735-309741, 309744, 309747, 309749,309751, 309753-309756, 309761-309762, 309764, 309767-309768, 309770,309772-309773, 309775-309777, 309781-309786, 309789, 309791-309797,309801-309806, 309809, 309811, 309813-309816, 309818-309819,309824-309834, 309841, 309844, 309847, 309850-309853, 309855-309871,309873-309875, 309881, 309885-309893, 309895-309897, 309899-309900,309902-309904, 309910, 309912, 309914-309915, 309919, 309921-309922,309924, 309926-309930, 309932-309939, 309944, 309946, 309949-309952,309955-309957, 309962, 309964-309965, 309967, 309970-309974,309978-309984, 309986-309989, 309991-309993, 310001, 310004-310006,310008, 310010-310012, 310014, 310017-310018, 310020, 310022-310023,310025-310028, 310034-310035, 310037-310038, 310045-310053,310055-310061, 310063, 310065, 310067, 310069, 310071, 310074,310076-310077, 310084, 310086-310088, 310093-310098, 310100,310102-310103, 310105-310107, 310110, 310112-310118, 310120-310125,310127-310128, 310130, 310132-310133, 310135-310136, 310138,310140-310143, 310145-310152, 310154-310159, 310161, 310163,310165-310168, 310171-310172, 310174, 310177-310184, 310193-310195,310199-310202, 310204-310205, 310207, 310209, 310214-310216, 310219,310221-310227, 310233-310234, 310236-310239, 310243, 310245-310247,310249-310250, 310252, 310254-310255, 310257, 310259, 310263,310265-310271, 310274, 310276, 310278, 310281, 310283, 310285, 310287,310289, 310291-310301, 310303, 310305-310310, 310312-310315,310317-310318, 310321-310322, 310324-310325, 310328-310330,310332-310334, 310336-310337, 310339-310343, 310345, 310348,310350-310353, 310357, 310359-310360, 310362, 310364, 310366-310367,310370-310371, 310373-310374, 310377-310378, 310382-310388,310390-310391, 310395-310401, 310404, 310407, 310409-310410,310414-310415, 310417-310419, 310421, 310427-310430, 310432-310436,310438, 310443-310445, 310447-310449, 310451-310455, 310458-310461,310465, 310467, 310472-310473, 310475-310478, 310481-310491,310493-310494, 310497-310501, 310504-310507, 310516-310518,310520-310522, 310525-310526, 310528-310534, 310536-310549,310552-310558, 310562-310564, 310566, 310568-310569, 310572,310576-310590, 310592-310595, 310597-310599, 310601, 310603-310604,310606, 310608-310609, 310613-310616, 310618-310620, 310622-310624,310628-310631, 310635-310636, 310640, 310642, 310644-310646,310649-310654, 310656-310659, 310661-310663, 310665-310670, 310672,310674, 310676, 310678, 310681, 310683, 310685-310686, 310688-310689,310691, 310693, 310695, 310697-310698, 310700, 310703, 310705-310708,310710, 310712-310713, 310715-310716, 310718, 310720-310722,310725-310729, 310731, 310734-310738, 310740-310742, 310744-310745,310747, 310749-310750, 310754-310763, 310765-310777, 310779-310783,310785-310789, 310791-310792, 310794-310797, 310799-310803,310805-310808, 310810-310818, 310820, 310822-310826, 310829-310834,310836-310837, 310842, 310845, 310847-310848, 310851, 310854-310864,310866, 310869-310870, 310872, 310875-310876, 310878, 310881-310882,310886-310889, 310891, 310893, 310896, 310898-310905, 310907,310910-310912, 310924-310929, 310933, 310936, 310938-310939,310941-310942, 310944-310948, 310951, 310953-310956, 310959-310960,310965-310966, 310968, 310970, 310972, 310974, 310980-310986,310988-310989, 310991, 310993-311002, 311004, 311006-311009,311012-311017, 311023, 311026, 311030-311033, 311036, 311039, 311041,311043-311053, 311060-311061, 311063-311067, 311069-311071,311073-311076, 311080-311081, 311084, 311086, 311088-311090,311092-311097, 311099-311106, 311109, 311111-311112, 311120-311129,311132, 311135-311136, 311138, 311140-311142, 311144-311147, 311151,311154-311156, 311159, 311161-311162, 311164-311169, 311173-311175,311179, 311181-311182, 311184-311185, 311187, 311191, 311193-311196,311199, 311201, 311203, 311205-311206, 311208-311209, 311214-311219,311221-311223, 311225-311229, 311231, 311233, 311239-311245, 311247,311249-311252, 311255, 311257-311262, 311264-311266, 311268-311271,311274-311285, 311289, 311292-311297, 311299-311301, 311304,311307-311309, 311311-311312, 311314-311315, 311317-311319, 311321,311323-311327, 311329-311330, 311333-311334, 311338-311343,311348-311350, 311352-311353, 311357, 311364, 311366, 311368-311371,311373, 311377-311380, 311382-311383, 311386-311387, 311392-311397,311399-311401, 311403-311405, 311407, 311410, 311413-311415, 311417,311422, 311424-311427, 311429-311430, 311432-311438, 311440-311442,311446-311450, 311452, 311454-311455, 311458-311459, 311461,311463-311464, 311466, 311468-311469, 311472-311480, 311482, 311484,311487-311497, 311501-311502, 311504-311506, 311508-311509,311512-311515, 311517, 311519-311522, 311524-311526, 311528-311530,311532-311533, 311535-311536, 311539, 311542-311546, 311550, 311552,311555-311556, 311558, 311560, 311564-311565, 311567, 311569-311571,311573-311575, 311582-311583, 311585-311591, 311594-311596,311599-311601, 311603-311607, 311609-311617, 311619-311620, 311622,311625, 311627-311628, 311630, 311633-311635, 311637-311642, 311646,311648, 311652-311653, 311655-311664, 311668-311669, 311671-311672,311676, 311681-311688, 311690-311691, 311693-311697, 311699-311703,311705, 311708-311710, 311713-311715, 311718, 311722-311732,311735-311738, 311742, 311745-311746, 311749-311750, 311752-311755,311758-311759, 311763-311767, 311769-311776, 311778, 311780-311785,311787, 311789-311795, 311798-311802, 311804, 311806-311810,311813-311816, 311818-311824, 311826-311834, 311837-311844,311850-311851, 311854-311856, 311858-311868, 311873, 311879, 311884,311886-311895, 311898, 311901, 311904-311905, 311907-311912, 311914,311920-311921, 311923-311925, 311927-311931, 311934, 311936,311938-311942, 311944, 311948, 311950-311953, 311956-311961,311964-311966, 311969-311970, 311972-311976, 311978, 311984, 311986,311990-311992, 311994, 311996-311997, 311999, 312001-312002,312004-312016, 312020-312021, 312023-312024, 312028-312029, 312031,312033-312034, 312036-312038, 312040-312041, 312048, 312051,312053-312057, 312060, 312062, 312064-312065, 312068-312071, 312073,312077-312078, 312081-312083, 312085, 312090-312095, 312097-312099,312102-312107, 312109, 312111-312116, 312118, 312121-312127,312129-312131, 312133, 312135-312137, 312139-312140, 312144-312149,312151, 312154-312155, 312158-312160, 312162-312163, 312166-312167,312170-312171, 312173-312174, 312176-312187, 312189, 312191,312193-312195, 312197-312198, 312200-312202, 312204, 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495472-495475,495478-495479, 495481-495487, 495491-495493, 495495-495496,495498-495499, 495502-495503, 495506-495508, 495510-495513, 495517,495519-495523, 495526-495528, 495531-495533, 495535-495537,495541-495544, 495546-495550, 495552-495556, 495558-495563,495566-495567, 495569-495583, 495585-495587, 495591, 495593-495594,495596-495597, 495600-495601, 495603-495609, 495613-495614, 495616,495620-495623, 495627, 495629-495637, 495639-495640, 495642-495661,495665, 495667-495668, 495670, 495676-495680, 495682-495685,495688-495693, 495695, 495699-495700, 495702, 495704-495708,495713-495715, 495718, 495721-495724, 495726, 495728-495729,495731-495732, 495734, 495737-495747, 495749-495750, 495758-495763,495768-495769, 495771, 495774-495777, 495784-495785, 495788-495789,495791-495795, 495797-495798, 495800-495804, 495807-495819, 495822,495826, 495828, 495836, 495839-495841, 495843, 495845, 495847,495849-495850, 495852, 495856, 495859-495861, 495863-495872,495875-495877, 495879-495886, 495888, 495892-495896, 495898-495918,495920-495921, 495924-495930, 495932-495939, 495942, 495944-495947,495952-495958, 495960, 495962-495963, 495965-495966, 495968-495969,495971, 495973, 495976, 495980-495981, 495983-495985, 495987,495989-495991, 495994-495995, 495999, 496001-496004, 496006-496007,496009-496015, 496017, 496019-496022, 496024-496028, 496030-496033,496035-496040, 496046-496047, 496049-496051, 496053-496056, 496059,496061, 496063, 496066, 496068-496069, 496071-496074, 496077-496080,496082-496083, 496087-496088, 496090-496091, 496093-496096,496100-496102, 496104-496105, 496109, 496111-496117, 496120,496125-496129, 496132-496134, 496139-496141, 496144-496149,496152-496155, 496157-496159, 496161-496164, 496166-496176,496180-496183, 496185-496191, 496193, 496195-496201, 496203-496206,496208, 496210-496212, 496214, 496216-496217, 496220-496221,496224-496226, 496230-496233, 496235-496236, 496238, 496240-496245,496249, 496251, 496254-496259, 496261-496262, 496264-496265, 496267,496269-496272, 496275-496276, 496278-496280, 496282, 496284-496285,496287-496291, 496294-496299, 496301, 496303, 496305-496307, 496310,496312, 496314-496318, 496320-496322, 496324, 496329-496330, 496332,496335-496337, 496340-496342, 496344-496345, 496348-496349,496351-496360, 496363-496364, 496366-496369, 496371, 496374,496376-496378, 496380-496389, 496391-496395, 496397-496401, 496404,496406-496407, 496409-496414, 496416-496420, 496422-496425,496427-496431, 496433, 496437, 496441, 496443-496461, 496463-496464,496466-496467, 496469-496471, 496473-496476, 496478-496479, 496482,496484-496486, 496488-496489, 496491, 496493-496494, 496497-496498,496501-496502, 496504-496506, 496508-496515, 496517, 496519-496522,496525-496526, 496528, 496531-496535, 496537, 496540-496541, 496543,496545-496552, 496554-496556, 496558-496564, 496568-496572, 496575,496578-496585, 496587, 496590-496591, 496594-496596, 496598-496601,496607-496609, 496612-496615, 496618-496621, 496623, 496625,496627-496628, 496631-496632, 496636-496645, 496648-496651,496653-496654, 496657, 496660, 496662-496665, 496667, 496669-496672,496677-496682, 496684-496695, 496697-496698, 496702-496703, 496705,496710-496713, 496715-496720, 496722, 496724-496728, 496731,496733-496739, 496741, 496745, 496747-496750, 496753-496763,496765-496766, 496769-496773, 496775, 496778, 496780, 496784-496787,496791-496792, 496794-496795, 496797, 496799-496800, 496803-496811,496814-496815, 496817-496822, 496825, 496828, 496830-496833, 496835,496839-496841, 496845, 496848-496849, 496851-496854, 496858,496860-496863, 496865-496868, 496870, 496872, 496874-496875,496879-496885, 496887, 496890, 496892-496896, 496898-496900,496902-496911, 496913-496914, 496916-496917, 496919-496921,496923-496930, 496932, 496935, 496938, 496940-496941, 496943-496944,496946-496948, 496953-496955, 496957-496958, 496960, 496962-496968,496973, 496975-496979, 496981-496986, 496989-496993, 496995-496997,496999-497002, 497005-497010, 497012, 497015-497023, 497025-497028,497030-497032, 497034-497037, 497039-497042, 497046-497051,497054-497060, 497062, 497066-497067, 497069-497071, 497073-497076,497080-497090, 497092, 497094-497097, 497099, 497101, 497105, 497107,497109, 497113-497115, 497117, 497120-497121, 497123, 497125-497126,497128, 497130, 497133-497140, 497142-497146, 497148-497162,497164-497167, 497171-497181, 497184, 497187-497189, 497193-497195,497197-497201, 497204-497208, 497211, 497217-497218, 497221-497225,497228-497231, 497233-497235, 497240, 497247-497252, 497254,497256-497263, 497266, 497268-497271, 497276, 497279, 497283-497289,497292-497293, 497295, 497298, 497300-497301, 497303-497306,497308-497310, 497313, 497315-497320, 497323-497324, 497327,497329-497333, 497339, 497341-497343, 497345-497362, 497364-497372,497374, 497378-497384, 497386-497389, 497392, 497394, 497396-497401,497403-497404, 497408, 497410-497412, 497418, 497424, 497426-497430,497432, 497434, 497436-497437, 497439, 497441, 497449, 497451-497459,497461-497462, 497467-497468, 497472-497476, 497478-497479,497481-497484, 497489, 497493-497496, 497498-497505, 497507-497512,497514-497533, 497535-497554, 497556-497562, 497564-497565, 497568,497570, 497572-497579, 497581, 497583-497588, 497591, 497593-497594,497596-497603, 497609-497614, 497616-497618, 497622-497624, 497626,497629-497630, 497632, 497636-497637, 497639-497640, 497644-497645,497649-497653, 497656-497657, 497661-497664, 497668, 497671-497673,497675-497679, 497681, 497684-497685, 497689, 497691, 497693-497696,497698-497699, 497701-497709, 497711-497712, 497714-497727

The foregoing written specification is considered to be sufficient toenable one skilled in the art to practice the invention. The presentinvention is not to be limited in scope by examples provided, since theexamples are intended as a single illustration of one aspect of theinvention and other functionally equivalent embodiments are within thescope of the invention. Various modifications of the invention inaddition to those shown and described herein will become apparent tothose skilled in the art from the foregoing description and fall withinthe scope of the appended claims. The advantages and objects of theinvention are not necessarily encompassed by each embodiment of theinvention.

1. A single stranded oligonucleotide having a sequence 5′-X-Y-Z, whereinX is any nucleotide, Y is a nucleotide sequence of 6 nucleotides inlength that is not a seed sequence of a human microRNA, and Z is anucleotide sequence of 1-23 nucleotides in length, wherein the singlestranded oligonucleotide is complementary with at least 8 consecutivenucleotides of a PRC2-associated region of a UTRN gene.
 2. The singlestranded oligonucleotide of claim 1, wherein the oligonucleotide doesnot comprise three or more consecutive guanosine nucleotides.
 3. Thesingle stranded oligonucleotide of claim 1, wherein the oligonucleotidedoes not comprise four or more consecutive guanosine nucleotides.
 4. Thesingle stranded oligonucleotide of claim 1, wherein the oligonucleotideis 8 to 30 nucleotides in length.
 5. The single stranded oligonucleotideof claim 1, wherein the oligonucleotide is 8 to 10 nucleotides in lengthand all but 1, 2, or 3 of the nucleotides of the complementary sequenceof the PRC2-associated region are cytosine or guanosine nucleotides. 6.The single stranded oligonucleotide of claim 1, wherein at least onenucleotide of the oligonucleotide is a nucleotide analogue.
 7. Thesingle stranded oligonucleotide of claim 6, wherein the at least onenucleotide analogue results in an increase in Tm of the oligonucleotidein a range of 1 to 5° C. compared with an oligonucleotide that does nothave the at least one nucleotide analogue.
 8. The single strandedoligonucleotide of claim 1, wherein at least one nucleotide of theoligonucleotide comprises a 2′ O-methyl.
 9. The single strandedoligonucleotide of claim 1, wherein each nucleotide of theoligonucleotide comprises a 2′ O-methyl.
 10. The single strandedoligonucleotide of claim 1, wherein the oligonucleotide comprises atleast one ribonucleotide, at least one deoxyribonucleotide, or at leastone bridged nucleotide.
 11. The single strand oligonucleotide of claim10, wherein the bridged nucleotide is a LNA nucleotide, a cEt nucleotideor a ENA modified nucleotide.
 12. The single stranded oligonucleotide ofclaim 1, wherein each nucleotide of the oligonucleotide is a LNAnucleotide.
 13. The single stranded oligonucleotide of claim 1, whereinthe nucleotides of the oligonucleotide comprise alternatingdeoxyribonucleotides and 2′-fluoro-deoxyribonucleotides.
 14. The singlestranded oligonucleotide of claim 1, wherein the nucleotides of theoligonucleotide comprise alternating deoxyribonucleotides and2′-O-methyl nucleotides.
 15. The single stranded oligonucleotide ofclaim 1, wherein the nucleotides of the oligonucleotide comprisealternating deoxyribonucleotides and ENA nucleotide analogues.
 16. Thesingle stranded oligonucleotide of claim 1, wherein the nucleotides ofthe oligonucleotide comprise alternating deoxyribonucleotides and LNAnucleotides.
 17. The single stranded oligonucleotide of claim 13,wherein the 5′ nucleotide of the oligonucleotide is adeoxyribonucleotide.
 18. The single stranded oligonucleotide of claim 1,wherein the nucleotides of the oligonucleotide comprise alternating LNAnucleotides and 2′-O-methyl nucleotides.
 19. The single strandedoligonucleotide of claim 18, wherein the 5′ nucleotide of theoligonucleotide is a LNA nucleotide.
 20. The single strandedoligonucleotide of claim 1, wherein the nucleotides of theoligonucleotide comprise deoxyribonucleotides flanked by at least oneLNA nucleotide on each of the 5′ and 3′ ends of thedeoxyribonucleotides.
 21. The single stranded oligonucleotide of claim1, further comprising phosphorothioate internucleotide linkages betweenat least two nucleotides.
 22. The single stranded oligonucleotide ofclaim 21, further comprising phosphorothioate internucleotide linkagesbetween all nucleotides.
 23. The single stranded oligonucleotide ofclaim 1, wherein the nucleotide at the 3′ position of theoligonucleotide has a 3′ hydroxyl group.
 24. The single strandedoligonucleotide of claim 1, wherein the nucleotide at the 3′ position ofthe oligonucleotide has a 3′ thiophosphate.
 25. The single strandedoligonucleotide of claim 1, further comprising a biotin moietyconjugated to the 5′ nucleotide.
 26. A single stranded oligonucleotidecomprising a region of complementarity that is complementary with atleast 8 consecutive nucleotides of a PRC2-associated region of a UTRNgene, wherein the oligonucleotide has at least one of: a) a sequencethat is 5′X-Y-Z, wherein X is any nucleotide and wherein X is anchoredat the 5′ end of the oligonucleotide, Y is a nucleotide sequence of 6nucleotides in length that is not a human seed sequence of a microRNA,and Z is a nucleotide sequence of 1 to 23 nucleotides in length; b) asequence that does not comprise three or more consecutive guanosinenucleotides; c) a sequence that has less than a threshold level ofsequence identity with every sequence of nucleotides, of equivalentlength to the second nucleotide sequence, that are between 50 kilobasesupstream of a 5′-end of an off-target gene and 50 kilobases downstreamof a 3′-end of the off-target gene; d) a sequence that is complementaryto a PRC2-associated region that encodes an RNA that forms a secondarystructure comprising at least two single stranded loops; and/or e) asequence that has greater than 60% G-C content.
 27. The single strandedoligonucleotide of claim 26, wherein the oligonucleotide has thesequence 5′X-Y-Z and wherein the oligonucleotide is 8-50 nucleotides inlength.
 28. A composition comprising a single stranded oligonucleotideof claim 1 and a carrier.
 29. A composition comprising a single strandedoligonucleotide of claim 1 in a buffered solution.
 30. A composition ofclaim 28, wherein the oligonucleotide is conjugated to the carrier. 31.The composition of claim 30, wherein the carrier is a peptide.
 32. Thecomposition of claim 30, wherein the carrier is a steroid.
 33. Apharmaceutical composition comprising a composition of claim 28 and apharmaceutically acceptable carrier.
 34. A kit comprising a containerhousing the composition of claim
 28. 35. A method of increasingexpression of a UTRN gene in a cell, the method comprising deliveringthe single stranded oligonucleotide of claim 1 into the cell.
 36. Themethod of claim 35, wherein delivery of the single strandedoligonucleotide into the cell results in a level of expression of a UTRNgene that is at least 50% greater than a level of expression of the UTRNgene in a control cell that does not comprise the single strandedoligonucleotide.
 37. A method increasing levels of a UTRN gene in asubject, the method comprising administering the single strandedoligonucleotide of any one of claim 1 to the subject.
 38. A method oftreating a condition associated with decreased levels of a UTRN gene ina subject, the method comprising administering the single strandedoligonucleotide of claim 1 to the subject.
 39. The method of claim 38,wherein the condition is a muscular dystrophy, including DMD, BMD, andmyotonic dystrophy.